CRAMP1 drives linker histone expression to enable Polycomb repression

Matthews, RE; Danac, JMC; Naden, EL; Farleigh Smith, LE; Lestari, S; Gungi, A; Appert, A; Buttress, T; Verma, A; Sinclair, O; Chong, F; Suberu, J; Antrobus, R; Bonev, B; Dawson, MA; Reid, AJ; Timms, RT; Ahringer, J; Tchasovnikarova, IA

Author(s): Matthews, RE; Danac, JMC; Naden, EL; Farleigh Smith, LE; Lestari, S; Gungi, A; Appert, A; Buttress, T; Verma, A; Sinclair, O; Chong, F; Suberu, J; Antrobus, R; Bonev, B; Dawson, MA; Reid, AJ; Timms, RT; Ahringer, J; Tchasovnikarova, IA;
Details: Publication Year 2025-07-03,Volume 85,Issue #13,Page 2503-2516
Journal Title: Molecular Cell
Publication Type: Research article
Abstract: In contrast to the well-understood role of core histones in DNA packaging, the function of the linker histone (H1) remains enigmatic. Challenging the prevailing view that linker histones are a general feature of heterochromatin, here we show a critical requirement for H1 in Polycomb repressive complex 2 (PRC2) function. A CRISPR-Cas9 genetic screen using a fluorescent PRC2 reporter identified an essential role for the poorly characterized gene CRAMP1 in PRC2-mediated repression. CRAMP1 localizes to the promoters of expressed H1 genes and positively regulates their transcription. CRAMP1 ablation simultaneously depletes all linker histones, which results in selective decompaction of H3K27me3-marked loci and derepression of PRC2 target genes without concomitant loss of PRC2 occupancy or enzymatic activity. Strikingly, we find that linker histones preferentially localize to genomic loci marked by H3K27me3 across diverse cell types and organisms. Altogether, these data demonstrate a prominent role for linker histones in epigenetic repression by PRC2.
Publisher: Cell Press
Keywords: *Histones/genetics/metabolism; *Polycomb Repressive Complex 2/genetics/metabolism; Animals; Humans; Mice; Promoter Regions, Genetic; Heterochromatin/genetics/metabolism; CRISPR-Cas Systems; *Epigenetic Repression; H1; Prc2; Polycomb; chromatin; epigenetic silencing; epigenetics; heterochromatin; histone; linker histone
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1016/j.molcel.2025.05.031
Open Access at Publisher's Site: https://doi.org/10.1016/j.molcel.2025.05.031
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-07-31 04:18:42

Last Modified: 2025-07-31 04:18:59