MYC and Chromatin

Thomas, Lance R.; Tansey, William P.

doi:10.11131/2015/101124

Cited by 5 publications

(3 citation statements)

References 181 publications

(223 reference statements)

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“…We identified ~900 peaks of MYC binding in G401 cells expressing the EGFP control (FDR of 0.01). This number of peaks was relatively low, compared to what has been reported for other cell types 33 , but the pattern of binding we observed was authentic for MYC. Binding sites were enriched in the E-box motif (Fig.…”

Section: Resultscontrasting

confidence: 58%

Inhibition of MYC by the SMARCB1 tumor suppressor

et al. 2019

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SMARCB1 encodes the SNF5 subunit of the SWI/SNF chromatin remodeler. SNF5 also interacts with the oncoprotein transcription factor MYC and is proposed to stimulate MYC activity. The concept that SNF5 is a coactivator for MYC, however, is at odds with its role as a tumor-suppressor, and with observations that loss of SNF5 leads to activation of MYC target genes. Here, we reexamine the relationship between MYC and SNF5 using biochemical and genome-wide approaches. We show that SNF5 inhibits the DNA-binding ability of MYC and impedes target gene recognition by MYC in cells. We further show that MYC regulation by SNF5 is separable from its role in chromatin remodeling, and that reintroduction of SNF5 into SMARCB1 -null cells mimics the primary transcriptional effects of MYC inhibition. These observations reveal that SNF5 antagonizes MYC and provide a mechanism to explain how loss of SNF5 can drive malignancy.

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Section: Resultscontrasting

confidence: 58%

Inhibition of MYC by the SMARCB1 tumor suppressor

et al. 2019

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“…The MYC family of oncogene transcription factors are overexpressed or deregulated in the majority of malignancies (1). The ability of MYC to regulate gene expression has been linked to its interaction with multiple chromatin regulators that are proposed to play important roles in each aspect of the transcription process (2). One chromatin regulator implicated in MYC function is the SWI/SNF chromatin remodeling complex, which is a large multi-subunit complex that uses the energy of ATP hydrolysis to alter contacts between histones and DNA (3,4).…”

Section: Introductionmentioning

confidence: 99%

Multiple interactions of the oncoprotein transcription factor MYC with the SWI/SNF chromatin remodeler

et al. 2021

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The SNF5 subunit of the SWI/SNF chromatin remodeling complex has been shown to act as a tumor suppressor through multiple mechanisms, including impairing the ability of the oncoprotein transcription factor MYC to bind chromatin. Beyond SNF5, however, it is unknown to what extent MYC can access additional SWI/SNF subunits or how these interactions affect the ability of MYC to drive transcription particularly in SNF5-null cancers. Here, we report that MYC interacts with multiple SWI/SNF components independent of SNF5. We show that MYC binds the pan-SWI/SNF subunit BAF155 through the BAF155 SWIRM domain, an interaction that is inhibited by the presence of SNF5. In SNF5-null cells, MYC binds with remaining SWI/SNF components to essential genes, although for a purpose that is distinct from chromatin remodeling. Analysis of MYC-SWI/SNF target genes in SNF5-null cells reveals that they are associated with core biological functions of MYC linked to protein synthesis. These data reveal that MYC can bind SWI/SNF in a SNF5-independent manner and that SNF5 modulates access of MYC to core SWI/SNF complexes. This work provides a framework in which to interrogate the influence of SWI/SNF on MYC function in cancers in which SWI/SNF or MYC are altered.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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“…Recognition of target genes by MYC is dependent on interaction with its obligate partner, MAX 2 , which creates a stable DNA-binding domain (DBD) that recognizes E-box motifs (CACGTG) in promoters and enhancers of MYC-regulated genes. Once bound to its target sites, MYC interacts with sets of cofactors 3 to modulate the gene expression patterns that ultimately lead to malignancy. Because of the pervasive involvement of MYC in human cancer, much interest is centered on identification of the partner proteins that MYC uses to control transcription, with the objective of identifying new interaction surfaces that can be pharmacologically exploited to kill cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif

et al. 2015

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The MYC family of oncogenes encodes a set of three related transcription factors that are overexpressed in many human tumors and contribute to the cancer-related deaths of more than 70,000 Americans every year. MYC proteins drive tumorigenesis by interacting with co-factors that enable them to regulate the expression of thousands of genes linked to cell growth, proliferation, metabolism, and genome stability. One effective way to identify critical cofactors required for MYC function has been to focus on sequence motifs within MYC that are conserved throughout evolution, on the assumption that their conservation is driven by protein-protein interactions that are vital for MYC activity. In addition to their DNA-binding domains, MYC proteins carry five regions of high sequence conservation known as Myc boxes (Mb). To date, four of the Myc box motifs (MbI, MbII, MbIIIa, and MbIIIb) have had a molecular function assigned to them, but the precise role of the remaining Myc box, MbIV, and the reason for its preservation in vertebrate Myc proteins, is unknown. Here, we show that MbIV is required for the association of MYC with the abundant transcriptional coregulator host cell factor 1 (HCF-1). We show that the invariant core of MbIV resembles the tetrapeptide HCF-binding motif (HBM) found in many HCF-interaction partners, and demonstrate that MYC interacts with HCF in a manner indistinguishable from the prototypical HBM-containing protein VP16. Finally, we show that rationalized point mutations in MYC that disrupt interaction with HCF-1 attenuate the ability of MYC to drive tumorigenesis in mice. Together, these data expose a molecular function for MbIV and indicate that HCF-1 is an important co-factor for MYC.

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MYC and Chromatin

Cited by 5 publications

References 181 publications

Inhibition of MYC by the SMARCB1 tumor suppressor

Inhibition of MYC by the SMARCB1 tumor suppressor

Multiple interactions of the oncoprotein transcription factor MYC with the SWI/SNF chromatin remodeler

Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif

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