H2A.Bbd: an X-chromosome-encoded histone involved in mammalian spermiogenesis

Abstract

Despite the identification of H2A.Bbd as a new vertebrate-specific replacement histone variant several years ago, and despite the many in vitro structural characterizations using reconstituted chromatin complexes consisting of this variant, the existence of H2A.Bbd in the cell and its location has remained elusive. Here, we report that the native form of this variant is present in highly advanced spermiogenic fractions of mammalian testis at the time when histones are highly acetylated and being replaced by protamines. It is also present in the nucleosomal chromatin fraction of mature human sperm. The ectopically expressed non-tagged version of the protein is associated with micrococcal nuclease-refractory insoluble fractions of chromatin and in mouse (20T1/2) cell line, H2A.Bbd is enriched at the periphery of chromocenters. The exceedingly rapid evolution of this unique X-chromosome-linked histone variant is shared with other reproductive proteins including those associated with chromatin in the mature sperm (protamines) of many vertebrates. This common rate of evolution provides further support for the functional and structural involvement of this protein in male gametogenesis in mammals.

Histone variants: dynamic punctuation in transcription

“…For example, H2A.B, first described as H2A.Bbd (Barr bodydeficient) has been found only in mammals. H2A.B is only ;50% identical to H2A and is rapidly evolving (Ishibashi et al 2010). The C terminus of H2A.B is 19 amino acids shorter than that of H2A, reducing the tail and part of the docking domain.…”

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

“…However, variants of H2A such as H2AL1/2, H2A.Bbd, or of H1, such as H1t2 and Hils1, are specifically incorporated during the histone-to-protamine exchange in round/elongating spermatids [70], [71], [72], [73]. While H2AL1/2 mark pericentric heterochromatin during spermatogenesis, they are quickly displaced from paternal heterochromatin after fertilization [74], potentially restricting a functional role in paternal inheritance.…”

“…While H2AL1/2 mark pericentric heterochromatin during spermatogenesis, they are quickly displaced from paternal heterochromatin after fertilization [74], potentially restricting a functional role in paternal inheritance. H2A.Bbd was found to destabilize nucleosomes, thus its presence in nucleosomes was suggested to facilitate replacement of histones by protamines [71]. Recently, another H2A variant, H2A.Lap1 has been shown to be loaded onto the X chromosome and autosomes in round spermatids and suggested to have a role in transcription of repressed genes [75].…”

H2A.B facilitates transcription elongation at methylated CpG loci

“…H2A.B is encoded by three copies of the H2AFB gene at the subtelomere region of the X chromosomes in both mice and humans. In mice, H2A.B1 and H2A.B2 (encoded by H2afb3 and H2afb2, respectively) are actively transcribed (Ishibashi et al 2010). H2A.B is a unique histone H2A variant that shares only 40%-50% sequence identity with canonical H2A (Chadwick and Willard 2001).…”