BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation

Marathe, Himangi; Watkins‐Chow, Dawn E.; Weider, Matthias; Hoffmann, Alana; Mehta, Gaurav; Trivedi, Archit; Aras, Shweta; Basuroy, Tupa; Mehrotra, Aanchal; Bennett, Dorothy C.; Pavan, William J.; Serna, Ivana L. de la

doi:10.1093/nar/gkx259

Cited by 56 publications

(97 citation statements)

References 82 publications

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“…Studying the effects of competing factors such as these would be an interesting area for future work. Furthermore, recent studies demonstrating that MITF and SOX10 can colocalize and recruit the chromatin remodeler BRG1 supports our findings (Laurette et al, ; Marathe et al, ). Finally, our BCDT model has learned that MYC‐MAX generally prefers more GC‐rich genomic regions compared to MITF (Figure ).…”

Section: Discussionsupporting

confidence: 92%

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Local genomic features predict the distinct and overlapping binding patterns of the bHLH‐Zip family oncoproteins MITF and MYC‐MAX

Hejna

Moon

Cheng

et al. 2018

Pigment Cell Melanoma Res

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MITF and MYC are well‐known oncoproteins and members of the basic helix–loop–helix leucine zipper (bHLH‐Zip) family of transcription factors (TFs) recognizing hexamer E‐box motifs. MITF and MYC not only share the core binding motif, but are also the two most highly expressed bHLH‐Zip transcription factors in melanocytes, raising the possibility that they may compete for the same binding sites in select oncogenic targets. Mechanisms determining the distinct and potentially overlapping binding modes of these critical oncoproteins remain uncharacterized. We introduce computational predictive models using local sequence features, including a boosted convolutional decision tree framework, to distinguish MITF versus MYC‐MAX binding sites with up to 80% accuracy genomewide. Select E‐box locations that can be bound by both MITF and MYC‐MAX form a separate class of MITF binding sites characterized by differential sequence content in the flanking region, diminished interaction with SOX10, higher evolutionary conservation, and less tissue‐specific chromatin organization.

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Section: Discussionsupporting

confidence: 92%

“…can colocalize and recruit the chromatin remodeler BRG1 supports our findings (Laurette et al, 2015;Marathe et al, 2017). Finally, our…”

Section: Discussionsupporting

confidence: 90%

Local genomic features predict the distinct and overlapping binding patterns of the bHLH‐Zip family oncoproteins MITF and MYC‐MAX

Hejna

Moon

Cheng

et al. 2018

Pigment Cell Melanoma Res

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“…To begin to evaluate the function of the three BAF60 isoforms in melanocyte differentiation, we assessed expression of BAF60A, BAF60B, and BAF60C in differentiating Melb‐a melanoblasts. As previously reported (Marathe et al, ), we found that pigmentation became visible after approximately 48 hr of differentiation (Figure 1a, top). BRG1 levels were fairly constant during differentiation, whereas MITF was expressed at a low level before differentiation and increased 12 hr after differentiation.…”

Section: Resultssupporting

confidence: 90%

BAF60A mediates interactions between the microphthalmia‐associated transcription factor and the BRG1‐containing SWI/SNF complex during melanocyte differentiation

Aras

Saladi

Basuroy

et al. 2018

Journal Cellular Physiology

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SWI/SNF chromatin remodeling enzymes are multisubunit complexes that contain one of two catalytic subunits, BRG1 or BRM and 9–11 additional subunits called BRG1 or BRM‐associated factors (BAFs). BRG1 interacts with the microphthalmia‐associated transcription factor (MITF) and is required for melanocyte development in vitro and in vivo. The subunits of SWI/SNF that mediate interactions between BRG1 and MITF have not been elucidated. Three mutually exclusive isoforms of a 60‐kDa subunit (BAF60A, B, or C) often facilitate interactions with transcription factors during lineage specification. We tested the hypothesis that a BAF60 subunit promotes interactions between MITF and the BRG1‐containing SWI/SNF complex. We found that MITF can physically interact with BAF60A, BAF60B, and BAF60C. The interaction between MITF and BAF60A required the basic helix‐loop‐helix domain of MITF. Recombinant BAF60A pulled down recombinant MITF, suggesting that the interaction can occur in the absence of other SWI/SNF subunits and other transcriptional regulators of the melanocyte lineage. Depletion of BAF60A in differentiating melanoblasts inhibited melanin synthesis and expression of MITF target genes. MITF promoted BAF60A recruitment to melanocyte‐specific promoters, and BAF60A was required to promote BRG1 recruitment and chromatin remodeling. Thus, BAF60A promotes interactions between MITF and the SWI/SNF complex and is required for melanocyte differentiation.

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“…(b) Overlap between peaks of SOX10 and TFAP2A binding in mouse melan-a cells. ChIP-seq data from SOX10 (Fufa et al, 2015), TFAP2A (Seberg et al, 2017) recruits BRG1 independently at some loci and in cooperation with MITF at others; the choice between these activities is presumably determined by other colocalizing factors (Laurette et al, 2015;Marathe et al, 2017). Different transcription factor combinations could result in the recruitment of different chromatin modifiers, analogous to the role of ZNF750 during skin differentiation (Boxer, Barajas, Tao, Zhang, & Khavari, 2014).…”

Section: Biochemical Mechanisms Remain To Be Determinedmentioning

confidence: 99%

Beyond MITF: Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma

Seberg

Otterloo

Cornell

2017

Pigment Cell Melanoma Res

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Summary MITF governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation. In addition, the level of MITF activity determines the phenotype adopted by melanoma cells, whether invasive, proliferative, or differentiated. However, MITF does not act alone. Here, we review literature on the transcription factors that co-regulate MITF-dependent genes. ChIP-seq studies have indicated that the transcription factors SOX10, YY1, and TFAP2A co-occupy subsets of regulatory elements bound by MITF in melanocytes. Analyses at single loci also support roles for LEF1, RB1, IRF4, and PAX3 acting in combination with MITF, while sequence motif analyses suggest that additional transcription factors colocalize with MITF at many melanocyte-specific regulatory elements. However, the precise biochemical functions of each of these MITF collaborators and their contributions to gene expression remain to be elucidated. Analogous to the transcriptional networks in morphogen-patterned tissues during embryogenesis, we anticipate that the level of MITF activity is controlled not only by the concentration of activated MITF, but also by additional transcription factors that either quantitatively or qualitatively influence the expression of MITF-target genes.

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BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation

Cited by 56 publications

References 82 publications

Local genomic features predict the distinct and overlapping binding patterns of the bHLH‐Zip family oncoproteins MITF and MYC‐MAX

Local genomic features predict the distinct and overlapping binding patterns of the bHLH‐Zip family oncoproteins MITF and MYC‐MAX

BAF60A mediates interactions between the microphthalmia‐associated transcription factor and the BRG1‐containing SWI/SNF complex during melanocyte differentiation

Beyond MITF: Multiple transcription factors directly regulate the cellular phenotype in melanocytes and melanoma

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