Histone supply: Multitiered regulation ensures chromatin dynamics throughout the cell cycle

Abstract

As the building blocks of chromatin, histones are central to establish and maintain particular chromatin states associated with given cell fates. Importantly, histones exist as distinct variants whose expression and incorporation into chromatin are tightly regulated during the cell cycle. During S phase, specialized replicative histone variants ensure the bulk of the chromatinization of the duplicating genome. Other non-replicative histone variants deposited throughout the cell cycle at specific loci use pathways uncoupled from DNA synthesis. Here, we review the particular dynamics of expression, cellular transit, assembly, and disassembly of replicative and non-replicative forms of the histone H3. Beyond the role of histone variants in chromatin dynamics, we review our current knowledge concerning their distinct regulation to control their expression at different levels including transcription, posttranscriptional processing, and protein stability. In light of this unique regulation, we highlight situations where perturbations in histone balance may lead to cellular dysfunction and pathologies.

The evolution and functional divergence of the histone H2B family in plants

“…In plants, histone H2Bs have undergone significant sequence divergence and expansion in the number of encoding genes [5,42]. In three distantly-related plant species-Arabidopsis thaliana (11), Marchantia polymorpha (6) and Klebsormidium nitens (3)-H2Bs vary substantially in the length and sequence of their N-terminal tails (S1A-S1C Fig) but not in the histone core domain (S2A and S2B Fig). This suggested that H2B proteins are highly diversified in plants, prompting us to assess evolutionary relationships across the plant kingdom.…”

“…Histone variants often differ by cell cycle or developmental stage-specific expression patterns [6][7][8]. For example, replicative histone H3.1/H3.2 are primarily incorporated into replicated chromatin during S-phase, whereas histone H3.3 functions as a replacement histone throughout the cell cycle during processes like transcription [2,[9][10][11][12][13][14][15]. CenH3/CENP-A is highly divergent from other H3 variants and is incorporated specifically within centromeric regions [16].…”

Interactions With Histone H3 & Tools to Study Them

“…H3.1 and H3.2 differ by a single amino acid at residue 96 ( Figure 1; Hake and Allis, 2006). Both are expressed in S-phase (Wu et al, 1982;Mendiratta et al, 2019) and deposited on replicating DNA (Tagami et al, 2004). They are, therefore, considered to be replication-coupled (RC) histones.…”

JMJD1B, a novel player in histone H3 and H4 processing to ensure genome stability

“…Histone synthesis is tightly coupled to DNA replication and peaks during the G1/S phase transition to account for doubling the genome. At this time, canonical histone genes are expressed, in contrast to histone variant genes, that are expressed at basal levels throughout the cell cycle [21,22]. Outside S-phase a histone pool is maintained in case of unanticipated changes to histone demand, such as DNA damage [9].…”