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

Chase M Woodley1, Alexander S Romer2, Jing Wang3,4

  • 1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.

Oncogene
|May 1, 2021
PubMed

Insights

MYC oncoprotein interacts with SWI/SNF components independently of SNF5, impacting gene transcription in SNF5-null cancers. SNF5 modulates MYC

Area of Science:

  • * Molecular Biology
  • * Cancer Biology
  • * Epigenetics

Background:

  • * The SNF5 subunit of the SWI/SNF complex suppresses tumors by inhibiting MYC binding to chromatin.
  • * The interaction of MYC with other SWI/SNF subunits and its impact on transcription in SNF5-null cancers remain largely unexplored.

Purpose of the Study:

  • * To investigate MYC interactions with SWI/SNF subunits independent of SNF5.
  • * To determine how these interactions affect MYC's transcriptional activity in SNF5-null cancers.
  • * To elucidate the role of SWI/SNF in MYC-driven transcription in the context of altered SWI/SNF or MYC.

Main Methods:

  • * Co-immunoprecipitation assays to detect MYC-SWI/SNF subunit interactions.
  • * Chromatin immunoprecipitation sequencing (ChIP-seq) to identify MYC and SWI/SNF binding sites on genes.
  • * Gene expression analysis to assess the functional consequences of MYC-SWI/SNF interactions.

Main Results:

  • * MYC interacts with multiple SWI/SNF components, including BAF155, independently of SNF5.
  • * SNF5 inhibits the binding of MYC to the BAF155 SWIRM domain.
  • * In SNF5-null cells, MYC binds SWI/SNF components to essential genes involved in protein synthesis, distinct from canonical chromatin remodeling functions.

Conclusions:

  • * MYC can associate with SWI/SNF complexes in an SNF5-independent manner.
  • * SNF5 acts as a modulator of MYC's access to core SWI/SNF complexes.
  • * This study provides a foundation for understanding SWI/SNF's influence on MYC function in cancers with SWI/SNF or MYC alterations.

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