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Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-022-29261-0

2041-1723

Carlos Rondón, Hun-Goo Lee, Anna Lappala, Danni Wang, Verónica Noches, Montserrat Olivares‐Costa, Marcela Sjöberg, Jeannie T. Lee, Marı́a Estela Andrés,

RNA modifications and cancer

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.