Oct1 is a switchable, bipotential stabilizer of repressed and inducible transcriptional states

Arvind Shakya1, Jinsuk Kang, Jeffrey Chumley

  • 1Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.

Insights

The Oct1 transcription factor acts as a switchable stabilizer, recruiting NuRD for repression or Jmjd1a to block repression and maintain poised gene expression states.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Epigenetics

Background:

  • The precise mechanisms by which Oct1 transcription factor regulates target gene expression remain largely unknown.
  • Understanding Oct1's role is crucial for deciphering gene expression control.

Purpose of the Study:

  • To elucidate how Oct1 influences gene expression by recruiting specific protein complexes.
  • To investigate Oct1's dual role in maintaining repressed and inducible gene states.

Main Methods:

  • Utilized murine fibroblasts, purified murine T cells, and a colon cancer cell line.
  • Analyzed target gene loci including Polr2a, Ahcy, Il2, and Cdx2.
  • Investigated the recruitment of Jmjd1a/KDM3A and the NuRD complex.

Main Results:

  • Oct1 recruits Jmjd1a/KDM3A to remove H3K9 dimethyl marks, blocking repression of Polr2a and Ahcy.
  • Oct1 recruits the NuRD complex to establish a repressed state at the Il2 and Cdx2 loci.
  • Oct1 can switch its function, recruiting Jmjd1a to block repression in a regulated manner.

Conclusions:

  • Oct1 acts as a switchable stabilizer, maintaining repressed states via NuRD and poised states via Jmjd1a.
  • Oct1 does not primarily trigger activation or repression but stabilizes existing states.

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