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Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin

Author

Listed:
  • Carlos Rivera

    (Pontificia Universidad Católica de Chile
    Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Hun-Goo Lee

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Anna Lappala

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Danni Wang

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Verónica Noches

    (Pontificia Universidad Católica de Chile)

  • Montserrat Olivares-Costa

    (Pontificia Universidad Católica de Chile)

  • Marcela Sjöberg-Herrera

    (Pontificia Universidad Católica de Chile)

  • Jeannie T. Lee

    (Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • María Estela Andrés

    (Pontificia Universidad Católica de Chile)

Abstract

RCOR1 is a known transcription repressor that recruits and positions LSD1 and HDAC1/2 on chromatin to erase histone methylation and acetylation. However, there is currently an incomplete understanding of RCOR1’s range of localization and function. Here, we probe RCOR1’s distribution on a genome-wide scale and unexpectedly find that RCOR1 is predominantly associated with transcriptionally active genes. Biochemical analysis reveals that RCOR1 associates with RNA Polymerase II (POL-II) during transcription and deacetylates its carboxy-terminal domain (CTD) at lysine 7. We provide evidence that this non-canonical RCOR1 activity is linked to dampening of POL-II productive elongation at actively transcribing genes. Thus, RCOR1 represses transcription in two ways—first, via a canonical mechanism by erasing transcriptionally permissive histone modifications through associating with HDACs and, second, via a non-canonical mechanism that deacetylates RNA POL-II’s CTD to inhibit productive elongation. We conclude that RCOR1 is a transcription rheostat.

Suggested Citation

  • Carlos Rivera & Hun-Goo Lee & Anna Lappala & Danni Wang & Verónica Noches & Montserrat Olivares-Costa & Marcela Sjöberg-Herrera & Jeannie T. Lee & María Estela Andrés, 2022. "Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29261-0
    DOI: 10.1038/s41467-022-29261-0
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