HILS1 is a spermatid-specific linker histone H1-like protein implicated in chromatin remodeling during mammalian spermiogenesis

Abstract

Chromatin remodeling is a major event that occurs during mammalian spermiogenesis, the process of spermatid maturation into spermatozoa. Nuclear condensation during spermiogenesis is accomplished by replacing somatic histones (linker histone H1 and core histones) and the testis-specific linker histone, H1t, with transition proteins and protamines. It has long been thought that H1t is the only testis-specific linker histone, and that all linker histones are replaced by transition proteins, and subsequently by protamines during spermiogenesis. Here, we report the identification and characterization of a spermatid-specific linker histone H1-like protein (termed HILS1) in the mouse and human. Both mouse and human HILS1 genes are located in intron 8 of the ␣-sarcoglycan genes. HILS1 is highly expressed in nuclei of elongating and elongated spermatids (steps 9 -15). HILS1 displays several biochemical properties that are similar to those of linker histones, including the abilities to bind reconstituted mononucleosomes, produce a chromatosome stop during micrococcal nuclease digestion, and aggregate chromatin. Because HILS1 is expressed in late spermatids that do not contain core histones, HILS1 may participate in spermatid nuclear condensation through a mechanism distinct from that of linker histones. Because HILS1 also belongs to the large winged helix͞forkhead protein superfamily, HILS1 may also regulate gene transcription, DNA repair, and͞or other chromosome processes during mammalian spermiogenesis.spermatogenesis ͉ transition nuclear proteins ͉ in silico subtraction ͉ genome database mining H istones are a family of basic proteins that organize eukaryotic DNA into a compact chromatin. There are five major classes of histones, the core histones H2A, H2B, H3, and H4, and the linker histones, H1. Two of each of the four core histones constitute an octamer unit of the nucleosome particle. H1 histones bind to DNA in the nucleosome and to the linker DNA between nucleosomes, thereby facilitating the compaction of nucleosomes into a 30-nm chromatin fiber and higher-order chromatin structures (1). These interactions between histones and DNA modulate gene activity, and both core and H1 histones have profound effects on transcription (2, 3). Among the five histone classes, H1 histones exhibit the most diversity. In mice and humans, there are eight previously described H1 subtypes, including the five somatic subtypes H1a-H1e, the replacement subtype H1o, the testis-specific linker-histone H1t (4-6), and the oocyte-specific H1 linker histone, H1foo (7). The genomic organizations of these histone H1 genes are conserved (8,9).Spermatogenesis is the process of development of male germ cells from spermatogonia to highly differentiated spermatozoa. During spermatogenesis, chromatin is restructured, and dramatic changes in histone gene expression are observed (10). In spermatogonia and preleptotene spermatocytes (cells undergoing DNA replication), the H1a and H1b linker histones are expressed (11). During meiotic prophase, striking ...

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.…”

“…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]. Among testis-specific H1 variants, it was shown that Hils1 localizes to the same sites as Tnp2 and Prm1 [73], while deficiency for H1t2 was found to result in reduced sperm mobility and condensation defects [72].…”

Comparative Analysis of Testis Protein Evolution in Rodents

“…The amount of functional information available for these rapidly evolving genes varies. Some genes have known roles in sperm-egg interaction (Acr, Howes et al 2001;Spa17, Richardson et al 1994;Spag8, Cheng et al 2007) or spermatogenesis (Hils1, Yan et al 2003). Another set of genes has inferred function on the basis of domain homology; a wide variety of functions are represented including receptor activity, DNA binding, and protein binding.…”

Testis-specific Linker Histone H1t Is Multiply Phosphorylated during Spermatogenesis

“…In spermatogonia and preleptotene spermatocytes, the linker histones H1a and H1b are expressed (6). When cells enter the meiotic prophase, somatic histones are partially replaced by testis-specific core histone variants, including TH2B, TH2A, and tH3 (6 -13) as well as by linker histone variants H1t (14), H1t2 (15), and HILS1 (16).…”