Yeast HMO1: Linker Histone Reinvented

Abstract

SUMMARY Eukaryotic genomes are packaged in chromatin. The higher-order organization of nucleosome core particles is controlled by the association of the intervening linker DNA with either the linker histone H1 or high mobility group box (HMGB) proteins. While H1 is thought to stabilize the nucleosome by preventing DNA unwrapping, the DNA bending imposed by HMGB may propagate to the nucleosome to destabilize chromatin. For metazoan H1, chromatin compaction requires its lysine-rich C-terminal domain, a domain that is buried between globular domains in the previously characterized yeast Saccharomyces cerevisiae linker histone Hho1p. Here, we discuss the functions of S. cerevisiae HMO1, an HMGB family protein unique in containing a terminal lysine-rich domain and in stabilizing genomic DNA. On ribosomal DNA (rDNA) and genes encoding ribosomal proteins, HMO1 appears to exert its role primarily by stabilizing nucleosome-free regions or “fragile” nucleosomes. During replication, HMO1 likewise appears to ensure low nucleosome density at DNA junctions associated with the DNA damage response or the need for topoisomerases to resolve catenanes. Notably, HMO1 shares with the mammalian linker histone H1 the ability to stabilize chromatin, as evidenced by the absence of HMO1 creating a more dynamic chromatin environment that is more sensitive to nuclease digestion and in which chromatin-remodeling events associated with DNA double-strand break repair occur faster; such chromatin stabilization requires the lysine-rich extension of HMO1. Thus, HMO1 appears to have evolved a unique linker histone-like function involving the ability to stabilize both conventional nucleosome arrays as well as DNA regions characterized by low nucleosome density or the presence of noncanonical nucleosomes.

Specialization of the Chromatin Remodeler RSC to Mobilize Partially-Unwrapped Nucleosomes

“…Hmo1 is an HMGB family protein that stabilizes fragile/partially-unwrapped nucleosomes, particularly at 184 rRNA and ribosomal protein gene promoters Struhl 2006, Panday andGrove 2017), and 185 thus might cooperate with RSC1 or RSC2 to promote remodeling. We first tested for rsc/hmo1 genetic 186 interactions by combining rsc1∆ or rsc2∆ with hmo1∆.…”

Long-range single-molecule mapping of chromatin accessibility in eukaryotes

“…Chromatin structure at the rDNA locus has long been known to adopt two distinct conformations [31][32][33] , depending on whether or not an individual unit is being transcribed. The active state is thought to be largely devoid of nucleosomes due to the extremely high levels of active transcription 32 ; the highmobility group protein Hmo1 is proposed to replace nucleosomes 30,34 . However, other studies have alternatively suggested that nucleosomes are found over actively transcribed rDNA arrays 35 .…”

HMGB Proteins from Yeast to Human. Gene Regulation, DNA Repair and Beyond

“…It has been demonstrated that in S. cerevisiae Hmo1 might replace histone H1 and protect linker DNA from nuclease digestion, creating a less dynamic chromatin environment that depends on its lysine-rich domain. This lysine-rich extension is unusual in other HMGB proteins, which have an acidic domain instead [101,102].…”