James M. Ntambi
Sep 1, 1999; 40:1549-1558
Reviews

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles

M el-Saadani
Apr 1, 1989; 30:627-630
Articles

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles

Oswald Quehenberger
Nov 1, 2010; 51:3299-3305
Research Articles

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

G Lepage
Jan 1, 1986; 27:114-120
Articles

JP Segrest
Feb 1, 1992; 33:141-166
Reviews

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles

John A. Glomset
Mar 1, 1968; 9:155-167
Reviews

JE Hixson
Mar 1, 1990; 31:545-548
Articles

Chatham House appoints Tim Benton as Research Director for Energy, Environment and Resources News Release sysadmin 30 May 2019

Chatham House is pleased to announce that Professor Tim Benton has been appointed as research director of the Energy, Environment and Resources Department.

Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security News Release sysadmin 27 June 2019

Chatham House is pleased to announce that Rob Yates has been appointed as head of the Centre on Global Health Security.

Creon Butler appointed to lead Global Economy and Finance Programme News Release sysadmin 22 October 2019

Creon Butler has been appointed to lead the Global Economy and Finance programme at Chatham House, joining the institute at the beginning of December. He will also form part of the institute’s senior leadership team.

Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy News Release sysadmin 18 November 2019

The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution.

Supporting Next Generation of Leaders in Sustainability News Release NCapeling 28 January 2021

A new programme offering paid internships for young people who are passionate about social, economic, and environmental sustainability has been launched.

The Implication of Greater Use of Investment Screening 26 June 2020 — 9:00AM TO 10:30AM Anonymous (not verified) 11 February 2021 Online

What is driving the trend towards greater use of investment screening by nation states and regional economic groupings?

• How is the COVID-19 crisis affecting this trend?
• What will the economic implications be?
• Will this help or hinder inclusivity and transparency in investment governance?
• Is there a role for international safeguards and/or international coordination of national/regional approaches to investment screening?

This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world.

A seat at the table – why inclusivity matters in global governance 10 May 2021 — 1:30PM TO 3:00PM Anonymous (not verified) 22 April 2021 Online

Exploring the changing dynamics of global cooperation and the role inclusivity can play in building collaborative action.

Please click on the below link to confirm your participation and receive your individual joining details from Zoom for this event. You will receive a confirmation email from Zoom, which contains the option to add the event to your calendar if you so wish.

The scale of today’s global challenges demand collaborative and coordinated action. But deepening geopolitical competition is threatening multilateralism while growing inequality and social tensions continue to undermine public confidence in the ability of international institutions to deliver.

Into this challenging environment, add the complexity and sheer pace of many global challenges such as the climate crisis and the proliferation of new technologies – issues that cannot be addressed effectively by governments alone.

• How do global institutions and mechanisms need to adapt to address the demands for a fairer distribution of power between states and to engage the diverse set of actors essential today for effective solutions?
• What can be learnt from existing initiatives that bring together governments, civil society, private sector, cities, next generation leaders and other stakeholders?
• And what are the political obstacles to greater inclusivity?

This event supports the launch of a synthesis paper from Chatham House’s Inclusive Governance Initiative.

Building trust in trade deals – is human rights monitoring the answer? 27 May 2021 — 4:00PM TO 5:15PM Anonymous (not verified) 14 May 2021 Online

Exploring the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running.

Please click on the below link to confirm your participation and receive your individual joining details from Zoom for this event. You will receive a confirmation email from Zoom, which contains the option to add the event to your calendar if you so wish.

The recent signing of the EU-China Investment Agreement has reignited arguments about trade and human rights. While many trade agreements envisage human rights monitoring in some shape or form, the monitoring systems that have emerged so far are not especially coherent, systematic or impactful. 

Are the human rights commitments in trade agreements more than just window-dressing?  If so, what kind of monitoring is needed to ensure they are lived up to? 

At this panel event, which marks the launch of a new Chatham House research paper, participants explore the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running in this context. 

• What factors are presently holding governments back, and where is innovation and investment most needed?
• What are the political, economic and structural conditions for fair and effective human rights monitoring of trade agreements? 
• Is human rights monitoring best done unilaterally – or should more effort be put into developing joint approaches? 
• What role might human rights monitoring have to play in governments’ strategies to ‘build back better’ from the COVID-19 pandemic?

Monitoring of trade deals needs a risk-based approach Expert comment NCapeling 24 May 2021

On human rights issues, trading partners must do more than trust to luck.

The recent row within the UK government about the treatment of agricultural products in a proposed new trade deal with Australia provides a reminder that changes to trading arrangements can have social and environmental costs, as well as benefits.

Although the UK government clearly feels political pressure to demonstrate its ‘Global Britain’ credentials with some speedily concluded new deals, rushing ahead without a full understanding of the social, environmental, and human rights implications risks storing up problems for later. In the meantime, calls for better evaluation and monitoring of trade agreements against sustainability-related commitments and goals – ideally with statutory backing – will only get stronger.

EU experiences with these kinds of processes are instructive. For more than 20 years the Directorate General for Trade of the European Commission (DG Trade) has been commissioning sustainability impact assessments (SIAs) from independent consultants in support of trade negotiations, and since 2012 these assessments have explicitly encompassed human rights impacts as a core part of the analysis.

These processes have since been augmented with a programme of periodic ‘ex post’ evaluations of trade agreements to ‘analyse the observed economic, social, human rights, and environmental impacts’ of live trade deals and to make recommendations about any mitigation action which may be needed.

For credibility and objectivity, the Commission outsources much of its sustainability assessment and ex post evaluation activities to independent consultants, who are encouraged to innovate and tailor their approaches subject to broad methodological parameters laid down by the Commission. Over time, experiences with specific assessment and monitoring assignments have enabled external SIA practitioners – and the Commission itself – to progressively strengthen these processes and underlying methodologies.

Yet despite the improvements there remains legitimate questions about whether the human rights aspects of these SIA processes – and subsequent evaluations – are having real policy impact. The difficulty of predicting human rights impacts of trade agreements in advance – as the COVID-19 crisis amply demonstrates – suggests a need for realism about the extent to which a ‘one off’ process, often carried out at a time when there is only ‘agreement in principle’ as to future trading terms, can produce a robust roadmap for heading off future human rights-related risks.

Human rights impact assessments have a potentially valuable role to play in laying down the substantive and structural foundations for future human rights monitoring as part of a broader, iterative, human rights risk management strategy. But the fragmented manner in which many trade agreements approach human rights issues, and the fact that outcomes are the product of negotiation rather than necessarily design, make it difficult to turn this vision into reality.

Controversies surrounding the SIA process for the EU-Mercosur agreement illustrate why striving for more coherence in the identification and subsequent management of human rights-related risks is important. In June 2019, the Commission decided to wrap up negotiations with the South America Mercosur bloc, even though the SIA process for the proposed agreement was still incomplete and the interim and final SIA reports yet to be delivered. Frustrated NGOs made their feelings clear in the form of a formal complaint – and a slap on the wrist from the EU Ombudsman duly followed.

However, when it eventually appeared in December 2020, the final SIA report for the EU-Mercosur deal did include a number of interesting recommendations for responding to specific areas of human rights-related risk identified through the pre-signing assessment process – such as flanking measures designed to address issues pertaining to health, equality, and protection of indigenous peoples, and stressing the need for ‘continuous monitoring’.

Hopefully these recommendations will be proactively followed up, but there are reasons not to be overly optimistic about that. To the extent that these recommendations might have required, or benefitted from, some tweaks to the terms of the trade agreement itself, it was clearly too late. And while there may be opportunities for EU institutions to follow up the recommendations through unilateral ex post evaluation processes, current legal, policy, and institutional arrangements provide few guarantees this will take place.

The credibility of the EU SIA programme has clearly taken a knock because of the problems with the EU-Mercosur process, and stakeholders could be forgiven for questioning whether expending time and effort on engaging in these processes is actually worthwhile. As a first step towards rectifying this, the Commission should be transparent about how it plans to respond to the EU-Mercosur SIA recommendations regarding flanking measures and follow up – ideally consulting with stakeholders about the various human rights monitoring options available.

Looking further ahead, the Commission should be urging SIA practitioners to deal more expansively with the options for follow up human rights monitoring in future SIA reports, setting out recommendations not just on the need for ongoing monitoring of human rights-related issues but on the detail of how this might be done, and how progress towards human rights-related goals could be tracked. And creativity should be encouraged because, as detailed in a newly-published Chatham House research paper, there may be more opportunities for human rights monitoring than first appear.

The SIA process could also provide a forum for exploring complementary measures needed to make future monitoring efforts as effective as possible – jointly and unilaterally; politically, structurally, and resources-wise; both within the framework of the trading relationship and extraneously. The credibility of the process – and hence stakeholder trust – would be further enhanced by commitments from the Commission to be more transparent in future about how different human rights monitoring recommendations laid out in SIAs have been taken into account in subsequent negotiations, in the supervisory arrangements developed for specific trading relationships, and in the implementation of EU trade policy more generally.

Counter-terrorism measures and sanctions: How to avoid negative consequences for humanitarian action? 9 September 2021 — 2:00PM TO 3:30PM Anonymous (not verified) 21 July 2021 Online

Exploring current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

Counter-terrorism measures  address broad forms of support to terrorist acts. Their expansion, internationally and domestically, has given rise to new points of friction with international humanitarian law. Unless the measures include adequate safeguards, they  can impede humanitarian action. Country-specific sanctions imposed for other objectives, such as ending conflicts or protecting civilians, raise similar challenges for humanitarian action. 

These problems are not new, but solutions at international and national level remain elusive. 

At this panel event, which marks the launch of a new Chatham House research paper, panellists explore current endeavours to address the tensions between counter-terrorism measures, sanctions and humanitarian action.

• What are the current dynamics and developments at Security Council level?  
• What are the opportunities now that the UK is developing its independent sanctions strategy? 
• What challenges do counter-terrorism requirements in funding agreements for humanitarian action  pose? 
• What is necessary to make progress?

Learnings must become practice as the Taliban return Expert comment NCapeling 7 September 2021

There is greater awareness of the adverse impact of counterterrorism measures and sanctions on humanitarian action. It is time to apply lessons learned.

The 9/11 attacks prompted the international community to adopt a wide range of counterterrorism measures. Debate continues over their compliance with international humanitarian law (IHL) and human rights law, and their effectiveness.

What has become clear is that some of these measures have made it difficult for humanitarian assistance to be provided to the millions of people living in areas under the control of armed groups designated as terrorist, or where such groups have a significant presence.

These include Al-Qaeda in Yemen’s Arabian peninsula, ISIL affiliates in Syria, Al Shabaab in Somalia, Boko Haram in Nigeria, Hamas in Gaza, and various Al-Qaeda affiliates in the Sahel. The lessons painfully learned need to be applied to Afghanistan under Taliban rule.

Impeding humanitarian work

Traditionally, legal counterterrorism measures criminalized acts of violence but, in recent years, measures adopted by the UN Security Council, the European Union (EU), and some states unilaterally, have expanded to address broader forms of support for terrorist acts and to groups designated as terrorist.

When these measures apply in situations of armed conflict – and in the absence of adequate safeguards – they can impede humanitarian organizations from operating as foreseen by IHL and in accordance with humanitarian principles, which require life-saving assistance to be provided in an impartial manner. Restrictions in sanctions imposed for policy objectives other than counterterrorism create similar tensions.

Prohibitions on making funds or other assets available directly or indirectly to persons or groups designated as terrorist can capture incidental payments made during humanitarian operations and relief consignments which are diverted and end up in the hands of these designated groups.

The most extreme restrictions cover the provision of medical assistance, in violation of the foundational principle of IHL that everyone who is wounded and sick – civilian or fighter – is entitled to medical care without discrimination, and those who provide it must not be punished.

Humanitarian organizations have been highlighting these problems for more than a decade. Recent developments give cause for cautious optimism that a turning point has been reached, as the bodies imposing counterterrorism measures and sanctions internationally and domestically have begun to demand compliance with international law and IHL.

In 2019 the UN Security Council unanimously issued a binding demand to member states to ensure all counterterrorism measures they adopt comply with obligations under international law, including IHL.

Recent renewals of UN country-specific sanctions have included similar demands with regards to measures taken by member states to give effect to them. Although this still falls short of an express exception for humanitarian action, it is a significant development, and a strong encouragement to include appropriate safeguards when implementing UN measures domestically.

Similar encouraging practice is discernible at EU level, and new domestic counterterrorism laws adopted by several states include safeguards for humanitarian action.

Applying lessons learned to Afghanistan

It is too soon to know what policies the Taliban will adopt, and the measures that the international community will take to promote compliance with IHL, human rights, and counterterrorism objectives. Nonetheless, policymakers implementing sanctions – and considering their expansion – cannot ignore their potential adverse impact on humanitarian action. They must bear in mind five key lessons.

First, there must be clarity on current legal restrictions, starting from who is designated under sanctions and counterterrorism measures. The UN Security Council has never designated the Taliban per se. Instead, it has listed ‘individuals, groups, undertakings and entities associated with the Taliban’. At present this list includes 135 individuals and five entities, four of which are ‘hawalas’ – money changers – the other being the Haqqani Network, a Sunni Islamist group.

UN financial sanctions require states to freeze the assets of designated persons and groups and ensure no funds, financial assets, or economic resources are made available to them, either directly or indirectly.

EU and UK sanctions simply replicate the restrictions and designations imposed by the UN, but the US has designated the Taliban as a ‘specially designated global terrorist’ which makes the Global Terrorism Sanctions Regulations applicable. These prohibit US nationals from making any contribution or provision of funds, goods, or services to, or for, the benefit of the Taliban.

Second, while listed individuals may play a role in the forthcoming Taliban administration, sanctions do not prohibit providing resources to a government department headed by a designated person.

There is a distinction between an individual and a department, and prohibitions in counterterrorism measures or sanctions on the provision of funds or other assets apply to the designated person, not to the department they may head.

Problems may arise if a designated person appropriates resources for personal benefit or to undermine policy objectives for which the sanctions were imposed. But this does not bring the department within the scope of the designation. Instead, the issue must be addressed from a prevention of diversion perspective.

Third, sanctions and counterterrorism measures must be designed so as to minimize their adverse impact on humanitarian action. One way of doing so is designating leadership figures rather than groups. The new US administration took this approach towards the Houthi in Yemen, with the designation of the group being revoked and new designations focusing on its leaders.

The chilling effect of sanctions is far broader than the actual restrictions they impose. Commercial actors in particular limit their activities in areas they perceive as high risk. In view of this, the effect of expanding existing designations to list the Taliban, now that it is in control of Afghanistan, would be to turn targeted sanctions into comprehensive ones.

In parallel, sanctions or counterterrorism measures should include express safeguards, which exclude funds, assets, and other support provided during humanitarian action from the restrictions – ideally in the form of exceptions or, if an option, general licences.

The adverse impact of the US Global Terrorism Sanctions has been limited until now, as only a small number of humanitarian actors subject to US measures operated in areas under Taliban control. This has now changed, and it is imperative the US issue a broad general licence to exclude assistance provided during humanitarian action from the sanctions.

Fourth, restrictions in funding agreements must not be more onerous than the underlying measures they aim to promote compliance with – in particular, they must not require screening or exclusion of final beneficiaries from the assistance they have been determined as requiring.

Finally, engagement with non-state armed groups for humanitarian purposes is essential for conducting operations effectively and safely, both for humanitarian organizations and the people they are trying to assist. Counterterrorism measures and sanctions do not prohibit such contact even when such groups or their members have been designated.

The past two decades have given states ample time to learn to avoid the adverse impact of sanctions and counterterrorism measures on humanitarian action. The people of Afghanistan deserve that these lessons now be applied.

Our research paper IHL and the humanitarian impact of counterterrorism measures and sanctions identifies the principal points of friction between these bodies of law, clarifies outstanding issues and misunderstandings, and offers practical recommendations for resolving tensions.

The UK must not sleepwalk into leaving the ECHR Expert comment NCapeling 17 March 2023

Talk of the UK leaving the European Convention on Human Rights (ECHR) keeps rearing its head with little thought for the real impact.

Withdrawal from the European Convention on Human Rights (ECHR) has not been firmly ruled out as a potential UK government policy option to allow easier implementation of its controversial new measures to deport asylum seekers to Rwanda. This, in the context of a UK general election looming and tackling the ‘small boats problem’ being one of the five priorities of UK prime minister Rishi Sunak.

In recent months, ECHR withdrawal has come up in relation to the UK’s controversial draft Illegal Migration Bill, the (now shelved) bill of rights, and – perhaps most significantly – the Northern Ireland Protocol deal with implications for the Good Friday Agreement. But leaving the ECHR – and likely the Council of Europe – would be counterproductive for the UK’s global leadership.

UK values and priorities will be undermined

The only other countries in the region outside of the Council of Europe, Russia and Belarus, both had sanctions imposed on them by the UK for their human rights record. Russia was expelled from the Council of Europe in 2022 due to its aggression in Ukraine and, although the UK would be deciding to remove itself from Europe’s oldest and largest intergovernmental human rights body, the optics would not be good.

This is especially true considering the UK’s vocal support for Ukraine in international forums, including its intervention in Ukraine’s case against Russia before the International Court of Justice and, potentially, in a separate case against Russia before the European Court of Human Rights itself.

More significantly and closer to home, the ECHR is a fundamental part of the Good Friday Agreement. It is difficult to argue UK withdrawal would not breach the agreement. As well as risking damage to intercommunal relations, such a breach is likely to significantly harm strategic relations with the US – and President Biden is set to visit Northern Ireland and the Republic of Ireland to mark the 25th anniversary of the Good Friday Agreement.

It would also damage relations with the UK’s closest neighbours, Ireland, and the European Union (EU), with whom the prime minister has only recently scored credits for securing the Northern Ireland Protocol deal. If the UK withdraws from the ECHR, the EU would be entitled to terminate important provisions concerning international law enforcement and judicial cooperation in criminal justice matters under Article 692 of the UK-EU Trade and Cooperation Agreement, further isolating the UK from allies who share its legal and other values.

Withdrawal would be in the name of sovereignty but with little thought to the practical implications on rights and few perceived gains from doing so. But the idea could easily gain traction by erroneously conflating the Strasbourg court and Council of Europe (of which the UK is a member) with the European Union (which the UK has left).

This means leaving the ECHR could easily be confused as a post-Brexit ‘tidy up’ exercise of taking back control from the EU when the reality is the UK would be withdrawing from a completely different regional body.

It would also be at odds with the UK’s Integrated Review Refresh which, reassuringly, contains references to the UK’s commitment to the rule of law, ‘respect for the fundamental principles of the UN Charter and international law’, and ‘universal human rights that underpins our democracy’. This would make the UK far less able to champion international law and influence states with long records of human rights violations, and run contrary to UK strategic priorities such as tackling aggression from Russia and China, its support for multilateralism, and its global legal leadership.

All this loss would come for little gain. Before going down this path, there must be a clearer understanding about exactly what concerns there are about the ECHR, and whether they stand up to scrutiny. Are they about UK sovereignty, specific issues about the European Court of Human Rights, or about the rights and obligations contained in the Convention?

The latter would raise a far bigger question on the UK’s commitment to other international treaties, such as the International Covenant on Civil and Political Rights and the UN Convention on Rights of the Child, as many ECHR obligations also exist elsewhere in both common law and international law.

The need for cool heads and a long-term view

The significant concerns surrounding proposals in the Illegal Migration bill have been well-documented, including in relation to obligations under the ECHR and UN Refugee Convention.

There are many reasons beyond simply human rights concerns which are preventing migrants being deported to Rwanda, including the fact there are insufficient countries with which the UK has agreements to allow for deportation.

Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential.

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.

The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA.

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Histone recognition by “reader” modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as “K4me3-R8me2a” and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 “K4me3-K9me3/2” bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 “K4me3-K9me3” peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 “K4me3-K9me3/2” bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.

A. Kh. Khachatryan, Kh. A. Khachatryan and A. Zh. Narimanyan
Trans. Moscow Math. Soc. 83 (), 183-200.
Abstract, references and article information

A. G. Sergeev, A. Kh. Khachatryan and Kh. A. Khachatryan
Trans. Moscow Math. Soc. 83 (), 55-65.
Abstract, references and article information

Korea's New Energy Policy and Implications for LNG Imports 3 October 2018 — 9:00AM TO 10:30AM Anonymous (not verified) 17 September 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The new energy policy of Moon Jae-In’s administration aims to swing radically from coal and nuclear towards renewables and LNG for power generation. During the last 12 months the priority given to the expansion of renewable energy has been overwhelming and the support for the expansion of gas not as strong as many observers had expected. The 13th gas supply and demand plan announced in Spring 2018 confirmed the trend. Based on this projection, Professor K. Paik will discuss how this new energy policy will affect Korea’s LNG imports strategy and what are the implications of Korea’s northern policy towards this LNG supply strategy and pipeline gas imports to the Korean Peninsula.

Attendance at this event is by invitation only.