Role of histones in male fertility

Role of histones in male fertility

Each Drosophila testis contains 6–12 germ stem cells (GSCs) that divide asymmetrically to produce gonialblast cells that undergo four transit-amplifying (TA) spermatogonial divisions before entering spermatocyte differentiation. Mechanisms governing these crucial transitions are not fully understood.

Researchers have identified the histone BigH1 as a key protein in stem cell differentiation to male sex cells. Histones are basic proteins that confer order and structure to DNA and they play an important role in gene regulation.

Depending on the stage of the process, histone BigH1 is either present and represses specific genes or it is inhibited to allow gene expression, thereby promoting differentiation, a process in which stem cells produce adult sex cells. When this delicate balance is lost, male Drosophila melanogaster show gonadal malformations and infertility.

"We hypothesize that BigH1 represses the genes that are not specific to the germ line (when stem cells give rise to sex cells). But we now have to unravel how it does this and how it is activated and silenced," says the group leader.

Authors show that dBigH1 is a general silencing factor that represses Bam, a key regulator of spermatogonia proliferation that is silenced in spermatocytes. Reciprocally, Bam represses dBigH1 during TA divisions.

This double-repressor mechanism switches dBigH1/Bam expression from off/on in spermatogonia to on/off in spermatocytes, regulating progression into spermatocyte differentiation. dBigH1 is also required for GSC maintenance and differentiation.

All animals have histones that are specific to the germ line. In Drosophila, BigH1 is expressed in the male and female germ lines. In contrast, variants of histone H1 differ between males and females in mice and in humans. "The histone BigH1, which we have studied in Drosophila melanogaster, shows most resemblance to the germ line variant of human females but it also shows some similarities to variants of the male germ line," explains first author of the paper in Cell Reports. "Because of these similarities, our work can contribute to our understanding of sex cell diferentiation in humans and help to explain some types of infertility," author adds.