The transcription elongation factor TCEA3 promotes the activity of the myogenic regulatory factors

PLoS One. 2019 Jun 3;14(6):e0217680. doi: 10.1371/journal.pone.0217680. eCollection 2019.

Abstract

The transcription elongation factor TFIIS is encoded by a three member gene family in vertebrates. Here we show that one member of this family, TCEA3, is upregulated during skeletal muscle differentiation and acts to promote gene activation by the myogenic regulatory family of transcription factors, which includes MyoD and myogenin. We show that myogenin is a direct regulator of Tcea3. Myogenin binds to the Tcea3 promoter and is required to recruit RNA polymerase II. TCEA3 can bind to both myogenin and MyoD and is co-recruited with the MRFs to promoters dependent on the MRFs. Depletion of myogenin inhibits the recruitment of TCEA3, suggesting that the interaction of TCEA3 with the MRFs serves to aid in recruitment to target promoters. Like TFIIS, we show that TCEA3 interacts with RNA polymerase II. TCEA3 travels with the elongating RNA polymerase II in the coding region of genes and depletions of TCEA3 inhibit the recruitment of RNA polymerase II to promoters. In proliferating cells, TCEA3 expressed at low levels and is present in both the nucleus and cytoplasm. However, upon differentiation, TCEA3 is upregulated and transported exclusively to the nucleus. Thus, our data show that TCEA3 is a required co-factor for MRF driven gene expression during myogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Humans
  • Mice
  • Muscles / metabolism
  • Myogenic Regulatory Factors / metabolism*
  • Organ Specificity / genetics
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Transport
  • RNA Polymerase II / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcriptional Elongation Factors / metabolism*

Substances

  • Myogenic Regulatory Factors
  • RNA, Messenger
  • Transcriptional Elongation Factors
  • transcription factor S-II
  • RNA Polymerase II