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Specific and redundant roles of TEAD transcription factors in C2C12 cell and primary myoblast differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE82193 | GEO | 2017/02/17

SECONDARY ACCESSION(S): PRJNA324273

REPOSITORIES: GEO

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Specific and redundant roles of TEAD transcription factors in C2C12 cell and primary myoblast differentiation (RNA-Seq)

Project description:Defining the function of TEAD transcription factors in myogenic differentiation has proved elusive due to overlapping expression and functional redundancy. Here, we show that siRNA silencing of either Tead1, Tead2 or Tead4 did not effect differentiation of primary myoblasts (PMs) while their simultaneous knockdown strongly impaired differentiation. In contrast in C2C12 cells, silencing of Tead1 or Tead4 impaired differentiation showing a differential requirement for these factors in PMs and C2C12 cells that involved both differential regulation of their expression and intracellular localisation. Through integration of Tead1 and Tead4 ChIP-seq with chromatin modifications, we identify active enhancers associated with genes activated during C2C12 cell differentiation that are bound by combinations of Tead4, Myod1 or Myog and show a signature of frequently co-occuring motifs. We show that distinct but overlapping sets of genes are deregulated by Tead silencing in C2C12 cells and PMs therefore describing for the first time in a comprehensive manner the specific and redundant regulatory roles of Tead factors in myogenic differentiation. We also performed ChIP-seq from mouse muscle in vivo identifying a set of highly transcribed muscle cell-identity genes and revealing that Tead4 binds a distinct repertoire of sites in C2C12 cells and muscle.

2017-02-17 | GSE82192 | GEO