Histone variants in pluripotency and disease

Abstract

SummaryMost histones are assembled into nucleosomes during replication to package genomic DNA. However, several variant histones are deposited independently of replication at particular regions of chromosomes. Such histone variants include cenH3, which forms the nucleosomal foundation for the centromere, and H3.3, which replaces histones that are lost during dynamic processes that disrupt nucleosomes. Furthermore, various H2A variants participate in DNA repair, gene regulation and other processes that are, as yet, not fully understood. Here, we review recent studies that have implicated histone variants in maintaining pluripotency and as causal factors in cancer and other diseases.

HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia

“…Interestingly, the eight alternative-spliced histones include genes encoding the H2A, H2B, and H4 subtypes but no H3 gene. However, histone variant H3.3 is already known to be expressed in nonproliferating cells (Urban and Zweidler 1983;Grove and Zweidler 1984;Pantazis and Bonner 1984;Brown et al 1985;Skene and Henikoff 2013). Indeed, substantial expression of genes encoding DNA replication-independent histone variant H3.3-H3F3A and H3F3B-was retained in RS and OIS cells ( Fig.…”

“…Histone H3.3 is enriched at nucleosomes at transcription start sites (TSSs) of genes and at enhancers and gene bodies of actively transcribed genes (Ahmad and Henikoff 2002;Jin et al 2009;Goldberg et al 2010). H3.3 differs from canonical histones H3.1 and H3.2 by four or five amino acids and is expressed constitutively throughout the cell cycle and in proliferating and nonproliferating cells from two genes: H3F3A and H3F3B (Skene and Henikoff 2013). The HIRA chaperone complex, comprised of HIRA/ UBN1/CABIN1, collaborates with histone-binding protein ASF1a to incorporate H3.3 into chromatin in a DNA replication-independent manner (Ray-Gallet et al 2002;Tagami et al 2004;Loppin et al 2005).…”

C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells

“…Histone variants usually modify the ability of nucleosomes to undergo remodeling (Apostolou and Hochedlinger, 2013). In particular, the histone variant macroH2A has previously been associated with resistance to efficient chromatin remodeling (Skene and Henikoff, 2013). In agreement, the presence of macroH2A potently inhibits transcription-factor-induced reprogramming of somatic cells to pluripotency by maintaining pluripotency loci in a repressed state (Barrero et al, 2013;GasparMaia et al, 2013;Pasque et al, 2012).…”

The Functional Topography of the Arabidopsis Genome Is Organized in a Reduced Number of Linear Motifs of Chromatin States

“…Another is the plethora of posttranslational modifications of histones that most frequently include acetylation, methylation, phosphorylation, and ubiquitination, among others (Berger, 2007;Kouzarides, 2007). Finally, individual histone molecules can be replaced within the nucleosome by histone variants such as H2A.Z and H3.3 with the aid of various histone chaperones and remodeling complexes (Filipescu et al, 2013;Skene and Henikoff, 2013). Altogether, these variations provide a very high combinatorial diversity at individual genomic loci (Berger, 2007;Kouzarides, 2007).…”