Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin

Carlos Rivera, Hun-Goo Lee, Anna Lappala, Danni Wang, Verónica Noches, Montserrat Olivares-Costa, Marcela Sjöberg-Herrera, Jeannie T. Lee () and María Estela Andrés ()
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Carlos Rivera: Pontificia Universidad Católica de Chile
Hun-Goo Lee: Massachusetts General Hospital
Anna Lappala: Massachusetts General Hospital
Danni Wang: Massachusetts General Hospital
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
María Estela Andrés: Pontificia Universidad Católica de Chile

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29261-0

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