Submitted April 13, 2007
Returned for revision May 30, 2007
Accepted July 18, 2007
Testis
Dynamic Regulation of Histone H3 Methylation at Lysine 4 in Mammalian Spermatogenesis
Maren Godmann ,
Veronik Auger ,
Vivian Ferraroni-Aguiar ,
Annarita Di Sauro ,
Claudio Sette ,
Ruediger Behr ,
and
Sarah Kimmins *
* To whom correspondence should be addressed. E-mail: sarah.kimmins{at}mcgill.ca.
Abstract
Spermatogenesis is a highly complex cell differentiation program governed by unique transcriptional regulation and massive chromatin alterations required for meiosis and post-meiotic 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. Histones can undergo methylation, acetylation and phosphorylation among other modifications on their N-terminus and these modifications can signal changes in chromatin structure. We have identified the temporal and spatial distribution of histone H3 mono-, di-, and tri-methylation at lysine 4 (K4), and the lysine-specific histone demethylase AOF2 (amine oxidase flavin containing, domain 2, previously known as LSD1) during mammalian spermatogenesis. These studies revealed a tightly regulated distribution for H3-K4 methylation and AOF2 and that H3-K4 methylation was highly similar between the mouse and the marmoset. In comparison to somatic tissues, AOF2 protein levels are greater in the testis. Distribution of AOF2 matches the cell- and stage-specific pattern of H3-K4 methylation. Interaction studies reveal unique epigenetic regulatory complexes associated with H3-K4 methylation in the testis including the association of AOF2 and MBD2a/b (methyl-CpG binding domain protein 2) in a complex with HDAC1 (histone deacetylase 1). These studies serve to enhance our understanding of epigenetic modifications and their roles in chromatin organization in male germ cell differentiation in normal and pathological states.
Key words:
Gamete Biology •
Testis •
Spermatogenesis •
Epigenetics •
Histones
