Histone Variants and Transcription Regulation

Abstract

Histones are the protein components of chromatin and are important for its organization and compaction. Although core histones are exclusively expressed during S phase of the cell cycle, there exist variants of canonical histones that are expressed throughout the cell cycle. These histone variants are often deposited at defined regions of the genome and they play important roles in a variety of cellular processes, such as transcription regulation, heterochromatin formation and DNA repair. In this chapter, we will focus on several histone variants that have been linked to transcription regulation, and highlight their physical and functional features that facilitate their activities in this context.

Chemical “Diversity” of Chromatin Through Histone Variants and Histone Modifications

“…Core or canonical histones are encoded by multiple copies of genes that do not contain introns and are transcribed into messenger RNAs (mRNAs) that contain special 3′ stemloops instead of the usual poly-A tails. The conserved stemloop structure at the 3′ ends of core histone mRNAs restricts their expression to S phase and, thus, ensures a supply of new histones for partnering with the newly synthesized DNA [8].…”

“…H3t and H3.5 are specifically found in the testes; the former has four additional amino acids compared to H3.1 and the latter has a~96 % sequence identity with H3.3. Finally, among all the H3 replacement variants, H3.3 is the most studied and best known for its association with active transcription (reviewed in [8]). More recently, species-specific H3 variants, such as H3.X and H3.Y, have also been found in some primates, but their functional roles are currently unclear [9].…”

“…Histone H2A has the largest family of variants including H2A.X, H2A.Z, macroH2A, and H2A.B (previously known as H2A.Bbd). Whereas H2A.Z and H2A.X are conserved throughout evolution, the other two members, macroH2A and H2A.B, are only found in vertebrates and mammals, respectively (reviewed in [8]). Given that these two histone variant families are the most studied, this review will focus on some of the newest findings on H3.3 and other H2A variants.…”

“…H2A.Z is an essential histone variant in complex eukaryotes and has been implicated in a variety of biological processes (reviewed in [8]). Similar to H3.3, H2A.Z is also encoded by two different genes (H2A.Z.1 and H2A.Z.2) that make distinct isoforms that differ by three amino acids.…”

“…The precise effect of H2A.Z's incorporation on nucleosome stability has been controversial with contrasting findings reported in the literature (reviewed in [8]). Part of the issue may be that the overall stability of H2A.Z-containing nucleosomes is also dependent on which other histone isoform, such as H3.1 or H3.3, is partnered with H2A.Z (further discussed later in this review).…”