A histone H3 methyltransferase controls epigenetic events required for meiotic prophase

Abstract

Epigenetic modifications of histones regulate gene expression and chromatin structure. Here we show that Meisetz (meiosis-induced factor containing a PR/SET domain and zinc-finger motif) is a histone methyltransferase that is important for the progression of early meiotic prophase. Meisetz transcripts are detected only in germ cells entering meiotic prophase in female fetal gonads and in postnatal testis. Notably, Meisetz has catalytic activity for trimethylation, but not mono- or dimethylation, of lysine 4 of histone H3, and a transactivation activity that depends on its methylation activity. Mice in which the Meisetz gene is disrupted show sterility in both sexes due to severe impairment of the double-stranded break repair pathway, deficient pairing of homologous chromosomes and impaired sex body formation. In Meisetz-deficient testis, trimethylation of lysine 4 of histone H3 is attenuated and meiotic gene transcription is altered. These findings indicate that meiosis-specific epigenetic events in mammals are crucial for proper meiotic progression.

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

“…In species from yeast to mammals, recombination hotspots correlate with enrichment for H3K4me3 [93], [94]. In mammals, these sites are bound by Prdm9 (also known as Meisetz), a protein capable of methylating H3K4 [95] and which is required for the completion of both male and female meiosis in mice [96]. It was shown that variations in hotspot usage correlate with variation in the DNA binding domain of Prdm9 [95], [97].…”

Single nucleotide polymorphisms in the SEPTIN12 gene may be associated with azoospermia by meiotic arrest in Japanese men

“…Nested PCR was performed using primers for each intronic region and 10-fold diluted first PCR products as templates. The initial PCR was performed in a final volume of 25 μl, consisting of genomic DNA (10 ng), dNTP (0.32 mM 20 cycles under the same conditions as above, except that 2 μl of 10-fold diluted first PCR products were used as templates. Nested PCR products were purified using a QIAquick PCR Purification kit (Qiagen; Tokyo, Japan), and direct sequencing of each product was conducted (Fig.…”

“…Several critical genes expressed in mouse meiosis, such as Dmc1, Fkbp6, Scp3 (Sycp3), Spo11, Msh4 and Msh5, Meisetz, Cdk2, and Hop2, have been identified by disruption experiments in embryonic stem cells [12][13][14][15][16][17][18][19][20][21][22]. In 2006, Lin et al identified 10 genes involved in human spermatogenesis by subtractive hybridization microarray analysis of mRNA expression in testicular tissue [23].…”

Identification d’une protéine-clé pour le contrôle des sites de recombinaison méiotique

“…Parmi les gènes présents dans l'intervalle contenant Dsbc1, Prdm9 est un candidat particulièrement intéressant. D'une part Prdm9 est exprimé spécifiquement lors de la prophase de méiose ; d'autre part son produit est une histone méthyltrans-férase qui catalyse la triméthylation de la lysine 4 de l'histone H3 (H3K4) [6]. Or, notre équipe a montré récemment que cette modification est associée à l'initiation de la recombinaison à des points chauds chez la souris [7].…”