Chromatin signatures of cancer

Morgan, Marc A.; Shilatifard, Ali

doi:10.1101/gad.255182.114

Cited by 188 publications

(175 citation statements)

References 141 publications

(186 reference statements)

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“…2A). H3K27 acetylation and methylation are mutually exclusive, and the acetyltransferase CBP/p300 complex and methyltransferase Polycomb repressive complex (PRC2) act in opposition to one another (24,25 decrease in H3K27ac, we analyzed the expression of CBP/p300 and PRC2 components in H3122-LR cells using qRT-PCR (Fig. 2B).The mRNA expression of CREBBP and EP300 were decreased in H3122-LR cells, suggesting that the global decrease in H3K27ac levels was at least partially due to the decreased expression of H3K27 acetyltransferase.…”

Section: Massive Enhancer Remodeling Accompanies Acquired Resistancementioning

confidence: 99%

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

et al. 2018

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Section: Massive Enhancer Remodeling Accompanies Acquired Resistancementioning

confidence: 99%

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

et al. 2018

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“…Recent cancer genome sequencing approaches of many types of primary tumors and cancer cell lines have revealed that MLL3 and MLL4/COMPASS are among the most frequently mutated genes in both solid tumors and hematological malignancies (Morgan and Shilatifard 2015). The MLL3 mutation or its deletion is found in hematological malignancies, including 15% of DLBCL, MDS, and AML (Mrozek 2008;Pasqualucci et al 2011;Zhang et al 2013).…”

Section: Mutations Of Mll3 and Mll4 Members Of The Compass Family Inmentioning

confidence: 99%

Epigenetics of hematopoiesis and hematological malignancies

Hu¹,

Shilatifard

2016

Genes Dev.

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140

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Hematological malignancies comprise a diverse set of lymphoid and myeloid neoplasms in which normal hematopoiesis has gone awry and together account for ∼10% of all new cancer cases diagnosed in the United States in 2016. Recent intensive genomic sequencing of hematopoietic malignancies has identified recurrent mutations in genes that encode regulators of chromatin structure and function, highlighting the central role that aberrant epigenetic regulation plays in the pathogenesis of these neoplasms. Deciphering the molecular mechanisms for how alterations in epigenetic modifiers, specifically histone and DNA methylases and demethylases, drive hematopoietic cancer could provide new avenues for developing novel targeted epigenetic therapies for treating hematological malignancies. Just as past studies of blood cancers led to pioneering discoveries relevant to other cancers, determining the contribution of epigenetic modifiers in hematologic cancers could also have a broader impact on our understanding of the pathogenesis of solid tumors in which these factors are mutated.

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“…Thus, caution should be used in equating the regulatory role of a chromatin-modifying enzyme to a particular histone PTM. Reflecting their key role in gene control, cancer genome sequencing studies revealed that chromatinmodulating enzymes are frequently mutated in human cancers (Laugesen and Helin 2014;Masliah-Planchon et al 2015;Morgan and Shilatifard 2015).…”

Section: Shmtmentioning

confidence: 99%

Undercover: gene control by metabolites and metabolic enzymes

2016

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To make the appropriate developmental decisions or maintain homeostasis, cells and organisms must coordinate the expression of their genome and metabolic state. However, the molecular mechanisms that relay environmental cues such as nutrient availability to the appropriate gene expression response remain poorly understood. There is a growing awareness that central components of intermediary metabolism are cofactors or cosubstrates of chromatin-modifying enzymes. As such, their concentrations constitute a potential regulatory interface between the metabolic and chromatin states. In addition, there is increasing evidence for a direct involvement of classic metabolic enzymes in gene expression control. These dual-function proteins may provide a direct link between metabolic programing and the control of gene expression. Here, we discuss our current understanding of the molecular mechanisms connecting metabolism to gene expression and their implications for development and disease.Metabolism and gene regulation are two fundamental biological processes that are essential to all living organisms. Homeostasis, cell growth, and differentiation all require the coordination of metabolic state and gene expression programs. Nevertheless, how expression of the genome adapts to metabolic state or environmental changes is not well understood. One level of regulation involves signal transduction pathways that control key transcription factors that act as master regulators of gene expression programs. In addition, post-translational modifications (PTMs) of chromatin play a major role in the activation or repression of gene transcription. These include acetylation, methylation, and phosphorylation of the histones and DNA methylation. Some of these chromatin modifications are involved in the maintenance of stable patterns of gene expression, usually referred to as epigenetic regulation. Pertinently, the activity of enzymes that modulate chromatin is critically dependent on central metabolites as cofactors or cosubstrates. Thus, the availability of metabolites that are required for the activity of histone-modifying enzymes may connect metabolism to chromatin structure and gene expression. Finally, selective metabolic enzymes act in the nucleus to adjust gene transcription in response to changes in metabolic state. Here, we review the interface between metabolism and gene transcription. We focus on the molecular mechanisms involved and discuss unresolved issues and implications for development and disease. The basics of metabolism and gene expression controlMetabolism is the total of all chemical reactions in cells and organisms that maintain life. Metabolism can be divided into two classes: catabolic processes (the breakdown of molecules that usually results in the release of energy) and anabolic processes (the synthesis of components such as proteins, lipids, and nucleic acids, which costs energy). Cellular (or intermediary) metabolism is organized in separate chemical pathways formed by a chain of linked enzymatic reactions in wh...

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Chromatin signatures of cancer

Cited by 188 publications

References 141 publications

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors

Epigenetics of hematopoiesis and hematological malignancies

Undercover: gene control by metabolites and metabolic enzymes

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