The missing linker: emerging trends for H1 variant-specific functions

Abstract

Major advances in the chromatin and epigenetics fields have uncovered the importance of core histones, histone variants and their post-translational modifications (PTMs) in modulating chromatin structure. However, an acutely understudied related feature of chromatin structure is the role of linker histone H1. Previous assumptions of the functional redundancy of the 11 nonallelic H1 variants are contrasted by their strong evolutionary conservation, variability in their potential PTMs, and increased reports of their disparate functions, sub-nuclear localizations and unique expression patterns in different cell types. The commonly accepted notion that histone H1 functions solely in chromatin compaction and transcription repression is now being challenged by work from multiple groups. These studies highlight histone H1 variants as underappreciated facets of chromatin dynamics that function independently in various chromatin-based processes. In this review, we present notable findings involving the individual somatic H1 variants of which there are seven, underscoring their particular contributions to distinctly significant chromatin-related processes.

Single Molecule Analysis of CENP-A Chromatin by High-Speed Atomic Force Microscopy

“…Thus, we extended this new type of HS-AFM analysis to another factor that is known to repress transcription. A prime candidate is the linker histone H1, which is known to efficiently compact H3 chromatin and restrict transcription (Clausell et al, 2009; Prendergast and Reinberg, 2021; Saha and Dalal, 2021). Previously we published HS-AFM movies of H3 chromatin and H3 chromatin with linker histone variant H1.5 (Melters and Dalal, 2021).…”

Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies

“…To which extent the latter could represent I compartments, similar to the ones described in activated B cells (29) remains to determined. Loss of H1 either in B or T lymphocytes was also shown to induce a profound reprogramming of epigenetic states with an expansion of H3K36me2 deposition at the expense of H3K27me3, suggesting that H1 binding plays an active role in balancing these modifications (203). Deletion of H1c and H1e in murine GC B cells conferred enhanced fitness and self-renewal, while at the molecular level inducing large-scale, but focal, chromatic decompaction and de-repression of stemness signature gene (202).…”

Molecular and Cellular Functions of the Linker Histone H1.2

“…Upon DNA damage, local changes to the condensation state of the chromatin are essential for the recruitment of the DNA damage repair factors. H1.2 has been shown to have a weaker ability to compact chromatin compared to most other variants, which endows H1.2 particular functions in DNA damage repair ( Orrego et al, 2007 ; Prendergast and Reinberg., 2021 ). It has been shown that ITCH mediated H1.2 K46 ubiquitination suppresses DNA damage repair by impairing RNF8/RNF168-dependent formation of 53BP1 foci, which is a crucial component of NHEJ (non-homologous end joining) signaling ( Chang et al, 2019 ).…”