Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin

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dc.contributor.authorRivera, Carlos
dc.contributor.authorLee, Hun-Goo
dc.contributor.authorLappala, Anna
dc.contributor.authorWang, Danni
dc.contributor.authorNoches, Veronica
dc.contributor.authorOlivares-Costa, Montserrat
dc.contributor.authorSjoberg-Herrera, Marcela
dc.contributor.authorLee, Jeannie T.
dc.contributor.authorAndres, Maria Estela
dc.date.accessioned2025-01-20T21:10:41Z
dc.date.available2025-01-20T21:10:41Z
dc.date.issued2022
dc.description.abstractThe classical neuronal-gene corepressor RCOR1/CoREST is paradoxically enriched in transcriptionally active chromatin. Here the authors show RCOR1 is recruited during promoter-proximal pausing and negatively regulates the nascent-transcript synthesis. They also show that an RCOR1-LSD1- HDAC1 complex removes lysine acetylation from RNA polymerase II to repress transcription.
dc.description.abstractRCOR1 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.
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41467-022-29261-0
dc.identifier.eissn2041-1723
dc.identifier.urihttps://doi.org/10.1038/s41467-022-29261-0
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93588
dc.identifier.wosidWOS:000772575300024
dc.issue.numero1
dc.language.isoen
dc.revistaNature communications
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleUnveiling RCOR1 as a rheostat at transcriptionally permissive chromatin
dc.typeartículo
dc.volumen13
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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