Understanding the Words of Chromatin Regulation

Wu, Jiang; Lessard, Julie; Crabtree, Gerald R.

doi:10.1016/j.cell.2009.01.009

Cited by 325 publications

(315 citation statements)

References 57 publications

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“…We provide evidence here that Chd7, c-Myc, and Given the complexity and dynamic nature of ES cell selfrenewal and open chromatin maintenance, alterations in the composition and activity of Ash2l complexes during ES cell differentiation warrant further investigation. One possible approach is to utilize advanced genomic and proteomic methods to systematically dissect Ash2l signaling networks and chromatin dynamics (65,66). Taken together, our results demonstrate that Ash2l is necessary for ES cell pluripotency and open chromatin regulation and carries out its function through multiple target proteins.…”

Section: Discussionmentioning

confidence: 67%

The Trithorax Group Protein Ash2l Is Essential for Pluripotency and Maintaining Open Chromatin in Embryonic Stem Cells

Wan

Liang

Xiong

et al. 2013

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 67%

The Trithorax Group Protein Ash2l Is Essential for Pluripotency and Maintaining Open Chromatin in Embryonic Stem Cells

Wan

Liang

Xiong

et al. 2013

Journal of Biological Chemistry

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“…Mammalian SWI/SNF complexes have been biochemically purified from different tissues and found to contain unique combinations of subunits depending upon cell type and developmental stage (32). Similarly, we predict that the C. elegans SWI/SNF subunits combine to form molecularly and functionally distinct complexes through the incorporation of different combinations of subunits (Fig.…”

Section: Resultsmentioning

confidence: 99%

SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans

Mathies¹,

Blackwell²,

Austin³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Alcohol abuse is a widespread and serious problem. Understanding the factors that influence the likelihood of abuse is important for the development of effective therapies. There are both genetic and environmental influences on the development of abuse, but it has been difficult to identify specific liability factors, in part because of both the complex genetic architecture of liability and the influences of environmental stimuli on the expression of that genetic liability. Epigenetic modification of gene expression can underlie both genetic and environmentally sensitive variation in expression, and epigenetic regulation has been implicated in the progression to addiction. Here, we identify a role for the switching defective/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in regulating the behavioral response to alcohol in the nematode Caenorhabditis elegans. We found that SWI/SNF components are required in adults for the normal behavioral response to ethanol and that different SWI/SNF complexes regulate different aspects of the acute response to ethanol. We showed that the SWI/SNF subunits SWSN-9 and SWSN-7 are required in neurons and muscle for the development of acute functional tolerance to ethanol. Examination of the members of the SWI/SNF complex for association with a diagnosis of alcohol dependence in a human population identified allelic variation in a member of the SWI/SNF complex, suggesting that variation in the regulation of SWI/SNF targets may influence the propensity to develop abuse disorders. Together, these data strongly implicate the chromatin remodeling associated with SWI/SNF complex members in the behavioral responses to alcohol across phyla.SWI/SNF | alcohol | C. elegans | chromatin remodeling | GWAS

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“…Frequent mutations throughout the gene sequence including multiple truncation mutations have been reported in ovarian (Jones et al 2010;Wiegand et al 2010), gynecological (Guan et al 2011b), bladder (Gui et al 2011), gastric (Wang et al 2011), breast (Mamo et al 2012), and endometrial cancers (Guan et al 2011a;Wiegand et al 2011), suggesting a role as a tumor suppressor. ARID1A encodes BAF250a, a nuclear protein and a key component of the SWI/SNF chromatin-remodeling complex that functions as a regulator of gene expression and chromatin dynamics (Wu et al 2009). However, to date, the mechanisms by which loss of ARID1A function contributes to cancer pathophysiology remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer

et al. 2012

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Endometrial cancer is the most common gynecological malignancy, with more than 280,000 cases occurring annually worldwide. Although previous studies have identified important common somatic mutations in endometrial cancer, they have primarily focused on a small set of known cancer genes and have thus provided a limited view of the molecular basis underlying this disease. Here we have developed an integrated systems-biology approach to identifying novel cancer genes contributing to endometrial tumorigenesis. We first performed whole-exome sequencing on 13 endometrial cancers and matched normal samples, systematically identifying somatic alterations with high precision and sensitivity. We then combined bioinformatics prioritization with high-throughput screening (including both shRNA-mediated knockdown and expression of wild-type and mutant constructs) in a highly sensitive cell viability assay. Our results revealed 12 potential driver cancer genes including 10 tumor-suppressor candidates (ARID1A, INHBA, KMO, TTLL5, GRM8, IGFBP3, AKTIP, PHKA2, TRPS1, and WNT11) and two oncogene candidates (ERBB3 and RPS6KC1). The results in the ''sensor'' cell line were recapitulated by siRNA-mediated knockdown in endometrial cancer cell lines. Focusing on ARID1A, we integrated mutation profiles with functional proteomics in 222 endometrial cancer samples, demonstrating that ARID1A mutations frequently co-occur with mutations in the phosphatidylinositol 3-kinase (PI3K) pathway and are associated with PI3K pathway activation. siRNA knockdown in endometrial cancer cell lines increased AKT phosphorylation supporting ARID1A as a novel regulator of PI3K pathway activity. Our study presents the first unbiased view of somatic coding mutations in endometrial cancer and provides functional evidence for diverse driver genes and mutations in this disease.

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Understanding the Words of Chromatin Regulation

Cited by 325 publications

References 57 publications

The Trithorax Group Protein Ash2l Is Essential for Pluripotency and Maintaining Open Chromatin in Embryonic Stem Cells

The Trithorax Group Protein Ash2l Is Essential for Pluripotency and Maintaining Open Chromatin in Embryonic Stem Cells

SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans

Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer

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