SWI/SNF Chromatin Remodeling Enzymes in Melanocyte Differentiation and Melanoma

Mehrotra, Aanchal; Mehta, Gaurav; Aras, Shweta; Trivedi, Archit; Serna, Ivana L. de la

doi:10.1615/critreveukaryotgeneexpr.2014007882

Cited by 22 publications

(19 citation statements)

References 95 publications

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“…For example, mutations in the SWI/SNF chromatin remodeling complex were found to be prevalent in many cancers, and the complex itself was suggested to function as a tumor suppressor (Gonzalez-Perez et al 2013;Shain and Pollack 2013). In both melanocytes and melanoma, the SWI/SNF complex interacts with master transcription factors and promotes cell differentiation and survival (Mehrotra et al 2014). In comparison, we showed that INO80 silencing reduces oncogenic transcription and selectively inhibits the growth of both BRAF and NRAS mutant melanoma cells but not primary melanocytes.…”

Section: Discussionmentioning

confidence: 74%

“…In addition, recent studies have revealed a complex involvement of epigenetic mechanisms in melanoma development and progression. Particularly, factors involved in chromatin regulation, such as the chromatin remodeling complexes, were found to play important roles in controlling the gene expression program in melanoma (van den Hurk et al 2012;Mehrotra et al 2014). The ATPdependent chromatin remodelers are capable of remodeling chromatin structure by sliding, ejecting, or exchanging nucleosomes and are therefore critically engaged in chromatin organization, accessibility, and gene regulation (Ho and Crabtree 2010;Piatti et al 2011).…”

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confidence: 99%

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INO80 governs superenhancer-mediated oncogenic transcription and tumor growth in melanoma

et al. 2016

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Superenhancers (SEs) are large genomic regions with a high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, a chromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNF ATPase, is elevated in melanoma cells and patient melanomas compared with normal melanocytes and benign nevi. Furthermore, Ino80 silencing selectively inhibits melanoma cell proliferation, anchorage-independent growth, tumorigenesis, and tumor maintenance in mouse xenografts. Mechanistically, Ino80 occupies >90% of SEs, and its occupancy is dependent on transcription factors such as MITF and Sox9. Ino80 binding reduces nucleosome occupancy and facilitates Mediator recruitment, thus promoting oncogenic transcription. Consistently, genes co-occupied by Ino80 and Med1 are selectively expressed in melanomas compared with melanocytes. Together, our results reveal an essential role of INO80-dependent chromatin remodeling in SE function and suggest a novel strategy for disrupting SEs in cancer treatment.

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Section: Discussionmentioning

confidence: 74%

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confidence: 99%

INO80 governs superenhancer-mediated oncogenic transcription and tumor growth in melanoma

et al. 2016

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“…Four families of ATPase-dependent chromatin-remodeling complexes have been characterized to date: SWI/SNF family (switching defective/sucrose non-fermenting), ISWI (imitation SWI) family, NURD (nucleosome remodeling and deacetylation)/Mi-2/CHD (chromodomain, helicase, DNA binding) family and INO80 (inositol requiring 80) family (7). These chromatin remodelers control a myriad of biological processes including cell growth, proliferation, survival, differentiation and function in a cell type-specific manner (2, 8, 9). The deregulation of chromatin remodeling complexes often leads to debilitating and fatal diseases including developmental deformity, inflammatory disease (10) and cancer (11).…”

Section: Introductionmentioning

confidence: 99%

BPTF Is Essential for T Cell Homeostasis and Function

Wang

et al. 2016

The Journal of Immunology

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Bromodomain PHD Finger Transcription Factor (BPTF), a ubiquitously expressed ATP-dependent chromatin-remodeling factor, is critical for epigenetically regulating DNA accessibility and gene expression. While BPTF is important for the development of thymocytes, its function in mature T cells remains largely unknown. By specifically deleting BPTF from late DN3/DN4 stage of developing T cells, we found that BPTF was critical for the homeostasis of T cells via a cell intrinsic manner. In addition, BPTF was essential for the maintenance and function of Treg cells. Treg cell-specific BPTF deletion led to reduced Foxp3 expression, increased lymphocyte infiltration in the non-lymphoid organs and a systemic autoimmune syndrome. These findings therefore reveal a vital role for BPTF in T and Treg cell function and immune homeostasis.

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“…Because this activity is fundamental to development, the complex is potentially a major target for control of tissue regeneration. The complex is ubiquitous and can support either activation or repression functions, in part because it exists in most mammalian cells in different configurations with respect to alternative subunits [3][4][5]. Very little is known about the role of alternative SWI/SNF configurations in control of lineage selection, especially in mesenchymal stem cells (MSC).…”

Section: Introductionmentioning

confidence: 99%

SWI/SNF-Mediated Lineage Determination in Mesenchymal Stem Cells Confers Resistance to Osteoporosis

Nguyen

Flowers

et al. 2015

Stem Cells

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Redirecting the adipogenic potential of bone marrow‐derived mesenchymal stem cells to other lineages, particularly osteoblasts, is a key goal in regenerative medicine. Controlling lineage selection through chromatin remodeling complexes such as SWI/SNF, which act coordinately to establish new patterns of gene expression, would be a desirable intervention point, but the requirement for the complex in essentially every lineage pathway has generally precluded selectivity. However, a novel approach now appears possible by targeting the subset of SWI/SNF powered by the alternative ATPase, mammalian brahma (BRM). BRM is not required for development, which has hindered understanding of its contributions, but knockdown genetics here, designed to explore the hypothesis that BRM‐SWI/SNF has different regulatory roles in different mesenchymal stem cell lineages, shows that depleting BRM from mesenchymal stem cells has a dramatic effect on the balance of lineage selection between osteoblasts and adipocytes. BRM depletion enhances the proportion of cells expressing markers of osteoblast precursors at the expense of cells able to differentiate along the adipocyte lineage. This effect is evident in primary bone marrow stromal cells as well as in established cell culture models. The altered precursor balance has major physiological significance, which becomes apparent as protection against age‐related osteoporosis and as reduced bone marrow adiposity in adult BRM‐null mice. Stem Cells 2015;33:3028–3038

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SWI/SNF Chromatin Remodeling Enzymes in Melanocyte Differentiation and Melanoma

Cited by 22 publications

References 95 publications

INO80 governs superenhancer-mediated oncogenic transcription and tumor growth in melanoma

INO80 governs superenhancer-mediated oncogenic transcription and tumor growth in melanoma

BPTF Is Essential for T Cell Homeostasis and Function

SWI/SNF-Mediated Lineage Determination in Mesenchymal Stem Cells Confers Resistance to Osteoporosis

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