H3K36 Trimethylation-Mediated Epigenetic Regulation is Activated by Bam and Promotes Germ Cell Differentiation During Early Oogenesis in Drosophila

Abstract

Epigenetic silencing is critical for maintaining germline stem cells in Drosophila ovaries. However, it remains unclear how the differentiation factor, Bag-of-marbles (Bam), counteracts transcriptional silencing. We found that the trimethylation of lysine 36 on histone H3 (H3K36me3), a modification that is associated with gene activation, is enhanced in Bam-expressing cells. H3K36me3 levels were reduced in flies deficient in Bam. Inactivation of the Set2 methyltransferase, which confers the H3K36me3 modification, in germline cells markedly reduced H3K36me3 and impaired differentiation. Genetic analyses revealed that Set2 acts downstream of Bam. Furthermore, orb expression, which is required for germ cell differentiation, was activated by Set2, probably through direct H3K36me3 modification of the orb locus. Our data indicate that H3K36me3-mediated epigenetic regulation is activated by bam, and that this modification facilitates germ cell differentiation, probably through transcriptional activation. This work provides a novel link between Bam and epigenetic transcriptional control.

Cloning and Expression Analysis of Two Kdm Lysine Demethylases in the Testes of Mature Yaks and Their Sterile Hybrids

“…In the present study, levels of H3K36me3 in cattle-yaks were significantly lower than those in yaks. Low levels of H3K36me3 have probably repressed meiosis and blocked germ cell differentiation in cattle-yaks [25,50]. Levels of KDM4B and H3K36me3 were both lower in cattle-yaks compared with yaks, and these results do not appear to be consistent with findings that the levels of H3K36me3 were significantly decreased after inducible expression of KDM4B [47].…”

“…The function of H3K36me3 is related to transcriptional activation [49]. In related studies, the level of H3K36me3 plays important roles in germ cell differentiation, somatic cell reprogramming, and chromosome recombination [25,47,50]. It was reported that normal methylation levels of H3K36me3 are required for spermatogenesis and sperm differentiation [25].…”

“…In related studies, the level of H3K36me3 plays important roles in germ cell differentiation, somatic cell reprogramming, and chromosome recombination [25,47,50]. It was reported that normal methylation levels of H3K36me3 are required for spermatogenesis and sperm differentiation [25]. The localization of H3K36me3 in mouse spermatocytes indicates that H3K36me3 plays an important role in meiotic recombination [50].…”

“…The domain conservation and expression profiles of KDM histone demethylases suggest that they might play important roles during gametogenesis [24]. A previous study discovered that the active gene associated with H3K36 trimethylation (H3K36me3) is related to germ cell differentiation [25]. The genes for H3K27me3 were involved in the processes of spermatogenesis and germ cell development.…”

Expression of the core promoter factors TATA box binding protein and TATA box binding protein‐related factor 2 in Drosophila germ cells and their distinct functions in germline development

“…As several regulators of histone modifications are essential for germline development (Clough et al, 2007;Mukai et al, 2015), we found that both CBP and HDAC1 preferentially interacted with MamoAF (Figure 1). Additionally, since CBP is responsible for H3K27ac (Creyghton et al, 2010;Stasevich et al, 2014;Tie et al, 2009) and HDAC1 is required for the deacetylation of H3K27ac (Tie et al, 2009), we can say that proper regulation of H3K27ac levels may play an essential role in germline development.…”