title: Aberrant levels of histone H3 acetylation induce spermatid anomaly in mouse testis.
abstract: Histone acetylation is involved in the regulation of chromatin structure and gene function. We reported previously that histone H3 acetylation pattern is subject to dynamic changes and limited to certain stages of germ cell differentiation during murine spermatogenesis, suggesting a crucial role for acetylation in the process. In the present study, we investigated the effects of hyper- and hypo-acetylation on spermatogenesis. Changes in acetylation level were induced by either in vivo administration of sodium phenylbutyrate, a histone deacetylase inhibitor, or by knockdown of histone acetyltransferases using short hairpin RNA plasmids transfection. Administration of sodium phenylbutyrate induced accumulation of acetylated histone H3 at lysine 9 and lysine 18 in round spermatids, together with spermatid morphological abnormalities and induction of apoptosis through a Bax-related pathway. Knockdown of steroid receptor coactivator 1, a member of histone acetyltransferases, but not general control of amino acid synthesis 5 nor elongator protein 3 by in vivo electroporation of shRNA plasmids, reduced acetylated histone H3 at lysine 9 in round spermatids, and induced morphological abnormalities. We concluded that the proper regulation of histone H3 acetylation levels is important for spermatid differentiation and complex chromatin remodeling during spermiogenesis.
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Dai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Endo
authors.forename: Naotaro
authors.initials: N
authors.lastname: Akiyama
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamamoto-Fukuda
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009929:Organ Size; D010654:Phenylbutyrates / Q000494:pharmacology; D013087:Spermatids / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology* / Q000648:ultrastructure
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases