Title : Haspin regulates transcription of key spermiogenesis genes
Abstract:
Haspin is a serine/threonine kinase that phosphorylates histone H3 at threonine 3 (H3T3ph). It is involved in chromosome alignment, centromeric cohesion and spindle stability, as well as in positioning of the Chromosomal Passenger Complex (CPC) at centromeres. H3T3ph is also part of a combinatorial modification pattern, termed PMM (H3T3ph-H3K4me3-H3R8me2), which is also detected during mitosis. This study focuses on the functional role of Haspin in mouse embryonic stem cells (mESCs) and adult testes. Ectopic overexpression (OE) or knockout (KO) of Haspin did not significantly alter the self-renewal or differentiation capabilities of mESCs. However, RNA sequencing experiments revealed that Haspin dosage affects the expression levels of several male gametogenesis genes, such as Scml2, Dazl, ZFY1/2 and Eif2s3y. Immunohistochemical analysis of mouse testes showed that the H3T3ph mark is detected initially only in mitotic spermatogonia. As the gonad develops and matures, the entire PMM modification pattern can be found in haploid spermatids. This spatiotemporal pattern indicates that H3T3ph, and as a consequence Haspin, is involved in regulating the spermatogenesis-spermiogenesis expression program, probably through a binary phospho-methyl switch.
