Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin

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.

Establishing a prediction model of severe acute mountain sickness using deep learning of support vector machine recursive feature elimination

“…As one of the members of sodium-calcium exchangers, SLC8A2 has been previously evidenced as a nuclear translocation regulator of HIF1A [35], which was signi cantly down-regulated upon SLC8A2 overexpression [36]. Our study indicated that SLC8A2 acts upstream of multiple hypoxia and/ or altitudesensitive miR targets, like RCOR1 (a transcription rheostat essential for normal myeloerythroid lineage differentiation) [37,38]; PRDM1 and LDB1(both are involved in high-altitude adaptation) [39,40]; and CASP3 (a member of hypoxia-activated mitochondrial apoptosis pathway) [41]. We noticed that, both hsa-miR-133a-3p and hsa-miR-133b-3p mediate the signals from SLC8A2 or DIP2B to SLC4A1, a biomarker of AMS, which was correlated with various AMS symptoms and plays important roles in CO 2 gas transport in erythrocytes [42].…”

Establishing a prediction model of severe acute mountain sickness using machine learning of support vector machine recursive feature elimination

“…As one of the sodium-calcium exchangers, SLC8A2 has been previously shown to be a nuclear translocation regulator of HIF1A 37 , which was significantly downregulated upon SLC8A2 overexpression 38 . Our study indicated that SLC8A2 acts upstream of multiple hypoxia-and/or altitude-sensitive miR targets, such as RCOR1 (a transcription rheostat essential for normal myeloerythroid lineage differentiation) 39,40 , PRDM1 and LDB1 (both are involved in high-altitude adaptation) 41,42 , and CASP3 (a member of the hypoxia-activated mitochondrial apoptosis pathway) 43 . We noticed that both www.nature.com/scientificreports/ hsa-miR-133a-3p and hsa-miR-133b-3p mediate the signals from SLC8A2 or DIP2B to SLC4A1, a biomarker of AMS, which was correlated with various AMS symptoms and plays important roles in CO 2 gas transport in erythrocytes 44 .…”

The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs

“…These, on the first sight, contradictory observations could be explained with HMG20A acting as rheostat and thereby fine-tuning the expression of highly transcribed genes. Such a function has been previously described for the NuRD complex 43 and RCOR1 of the BHC/CoREST complex 44 . It is therefore tempting to speculate that HMG20A – among other functional outputs – works together with these complexes to dampen transcription of genes during differentiation.…”