Dynamic regulation of histone h3 methylation at lysine 4 in mammalian spermatogenesis

被引:114
作者
Godmann, Maren
Auger, Veronik
Ferraroni-Aguiar, Vivian
Di Sauro, Annarita
Sette, Claudio
Behr, Ruediger
Kimmins, Sarah
机构
[1] McGill Univ, Dept Anim Sci, Montreal, PQ H9X 3V9, Canada
[2] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H9X 3V9, Canada
[3] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, I-00133 Rome, Italy
[4] Fdn Santa Lucia, IRCCS, Lab Neuroembryol, I-00133 Rome, Italy
[5] German Primate Ctr, Stem Cell Res Grp, D-37077 Gottingen, Germany
关键词
AOF2/LSD; 7; epigenetics; gamete biology; histone epigenetics; spermatogenesis; testis;
D O I
10.1095/biolreprod.107.062265
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Spermatogenesis is a highly complex cell differentiation process that is governed by unique transcriptional regulation and massive chromatin alterations, which are required for meiosis and postmeiotic maturation. The underlying mechanisms involve alterations to the epigenetic layer, including histone modifications and incorporation of testis-specific nuclear proteins, such as histone variants and protamines. Histories can undergo methylation, acetylation, and phosphorylation among other modifications at their N-terminus, and these modifications can signal changes in chromatin structure. We have identified the temporal and spatial distributions of histone H3 mono-, di-, and trimethylation at lysine 4 (K4), and the lysine-specific histone demethylase AOF2 (amine oxidase flavin-containing domain 2, previously known as LSD1) during mammalian spermatogenesis. Our results reveal tightly regulated distributions of H3-K4 methylation and AOF2, and that H3-K4 methylation is very similar between the mouse and the marmoset. The AOF2 protein levels were found to be higher in the testes than in the somatic tissues. The distribution of AOF2 matched the cell- and stage-specific patterns of H3-K4 methylation. Interaction studies revealed unique epigenetic regulatory complexes associated with H3-K4 methylation in the testis, including the association of AOF2 and methyl-CpG-binding domain protein 2 (MBD2a/b) in a complex with histone deacetylase 1 (HDAC1). These studies enhance our understanding of epigenetic modifications and their roles in chromatin organization during male germ cell differentiation in both normal and pathologic states.
引用
收藏
页码:754 / 764
页数:11
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