Histone-binding domains: Strategies for discovery and characterization

Wilkinson, Alex W.; Gozani, Or

doi:10.1016/j.bbagrm.2014.01.007

Cited by 20 publications

(17 citation statements)

References 69 publications

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“…Analogous reader domains exist for binding to other histone modifications. For example, ten distinct domains have been found to govern binding of proteins to methyl-histones [68]. We will limit our discussion to acetyl-lysine readers.…”

Section: Acetyl-lysine Readers and Fibrosismentioning

confidence: 99%

Epigenetic regulation of cardiac fibrosis

Stratton

McKinsey

2016

Journal of Molecular and Cellular Cardiology

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Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases.

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Section: Acetyl-lysine Readers and Fibrosismentioning

confidence: 99%

Epigenetic regulation of cardiac fibrosis

Stratton

McKinsey

2016

Journal of Molecular and Cellular Cardiology

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“…Methylation events generally function through the modulation of protein-protein interactions (Wilkinson and Gozani 2014). We sought to identify candidate methyl-sensitive binding partners of MAPKAPK3-K355me1.…”

Section: Mapkapk3 Inhibition and Pdac Developmentmentioning

confidence: 99%

Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer

et al. 2016

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with few therapeutic options. We found that levels of the lysine methyltransferase SMYD2 (SET and MYND domain 2) are elevated in PDAC and that genetic and pharmacological inhibition of SMYD2 restricts PDAC growth. We further identified the stress response kinase MAPKAPK3 (MK3) as a new physiologic substrate of SMYD2 in PDAC cells. Inhibition of MAPKAPK3 impedes PDAC growth, identifying a potential new kinase target in PDAC. Finally, we show that inhibition of SMYD2 cooperates with standard chemotherapy to treat PDAC cells and tumors. These findings uncover a pivotal role for SMYD2 in promoting pancreatic cancer.

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“…Lysines can be mono-, di- or tri-methylated and the degree and specificity of methylation is exquisitely regulated by a combination of enzymatic specificity of KMTs/KDMs and their expression and recruitment mechanism to chromatin. Several chromatin-binding proteins can bind to these methylated lysine residues through their methyl lysine-binding motifs [54] and target the recruitment of regulatory proteins through their protein-protein interactions [31]. …”

Section: Histone Methylationmentioning

confidence: 99%

Regulation of histone methylation by noncoding RNAs

Joh

Palmieri

Hill

et al. 2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Cells can adapt to their environment and develop distinct identities by rewiring their transcriptional networks to regulate the output of key biological pathways without concomitant mutations to the underlying genes. These alterations, called epigenetic changes, persist stably through mitotic or, in some instances, meiotic cell divisions. In eukaryotes, heritable changes to chromatin structure are a prominent, but not exclusive, mechanism by which epigenetic changes are mediated. These changes are initiated by sequence-specific events, which trigger a cascade of molecular interactions resulting in feedback mechanisms, alterations in chromatin structure, histone posttranslational modifications (PTMs), and ultimately establishment of distinct transcriptional states. In recent years, advances in next generation sequencing have led to the discovery of several novel classes of noncoding RNAs (ncRNAs). In addition to their well-established cytoplasmic roles in posttranscriptional regulation of gene expression, ncRNAs have emerged as key regulators of epigenetic changes via chromatin-dependent mechanisms in organisms ranging from yeast to man. They function by affecting chromatin structure, histone PTMs, and the recruitment of transcriptional activating or repressing complexes. Among histone PTMs, lysine methylation serves as the binding substrate for the recruitment of key protein complexes involved in regulation of genome architecture, stability, and gene expression. In this review, we will outline the known mechanisms by which ncRNAs of different origins regulate histone methylation, and in doing so contribute to a variety of genome regulatory functions in eukaryotes.

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Histone-binding domains: Strategies for discovery and characterization

Cited by 20 publications

References 69 publications

Epigenetic regulation of cardiac fibrosis

Epigenetic regulation of cardiac fibrosis

Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer

Regulation of histone methylation by noncoding RNAs

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