1. Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin.
- Author
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Rivera C, Lee HG, Lappala A, Wang D, Noches V, Olivares-Costa M, Sjöberg-Herrera M, Lee JT, and Andrés ME
- Subjects
- Acetylation, Methylation, Protein Processing, Post-Translational, Transcription, Genetic, Chromatin genetics, RNA Polymerase II genetics, RNA Polymerase II metabolism
- 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., (© 2022. The Author(s).)
- Published
- 2022
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