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Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline.

Sin HS, Kartashov AV, Hasegawa K, Barski A, Namekawa SH - BMC Biol. (2015)

Bottom Line: Induction of late spermatogenesis genes during spermatogenesis is facilitated by poised chromatin established in the stem cell phases of spermatogonia, whereas silencing of somatic/progenitor genes during meiosis and postmeiosis is associated with formation of bivalent domains which also allows the recovery of the somatic/progenitor program after fertilization.Importantly, during spermatogenesis mechanisms of epigenetic regulation on sex chromosomes are different from autosomes: X-linked somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation without deposition of H3K27me3.Our results suggest that bivalent H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which maintain bivalent domains that are silent throughout the reproductive cycle), but also underlie reversible silencing of somatic/progenitor genes during the mitosis-to-meiosis transition in late spermatogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

ABSTRACT

Background: The male germline transcriptome changes dramatically during the mitosis-to-meiosis transition to activate late spermatogenesis genes and to transiently suppress genes commonly expressed in somatic lineages and spermatogenesis progenitor cells, termed somatic/progenitor genes.

Results: These changes reflect epigenetic regulation. Induction of late spermatogenesis genes during spermatogenesis is facilitated by poised chromatin established in the stem cell phases of spermatogonia, whereas silencing of somatic/progenitor genes during meiosis and postmeiosis is associated with formation of bivalent domains which also allows the recovery of the somatic/progenitor program after fertilization. Importantly, during spermatogenesis mechanisms of epigenetic regulation on sex chromosomes are different from autosomes: X-linked somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation without deposition of H3K27me3.

Conclusions: Our results suggest that bivalent H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which maintain bivalent domains that are silent throughout the reproductive cycle), but also underlie reversible silencing of somatic/progenitor genes during the mitosis-to-meiosis transition in late spermatogenesis.

No MeSH data available.


Active marks remain after the inactivation of autosomal somatic/progenitor genes in PS. a Distribution of histone marks around PS/RS inactive Vim gene locus and PS active Sycp3 gene locus in PS. b ATD of active marks at the active genes in PS. c ATD of active marks at the silent genes in PS. d ATD of active marks in PS. These genes are activated in RS. e ATD of each silent mark in representative groups in PS. ATD, average tag density; PS, pachytene spermatocytes; RS, round spermatids
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Fig4: Active marks remain after the inactivation of autosomal somatic/progenitor genes in PS. a Distribution of histone marks around PS/RS inactive Vim gene locus and PS active Sycp3 gene locus in PS. b ATD of active marks at the active genes in PS. c ATD of active marks at the silent genes in PS. d ATD of active marks in PS. These genes are activated in RS. e ATD of each silent mark in representative groups in PS. ATD, average tag density; PS, pachytene spermatocytes; RS, round spermatids

Mentions: Next, we sought to examine how the meiosis-specific transcriptome is regulated for autosomes during the PS stage. At the PS active gene synaptonemal complex protein 3 (Sycp3), active modifications such as H3K4me3, H4K8ac, H4K16ac, and Kcr were highly accumulated at the TSS, and H3K4me2 exhibited a broader peak of enrichment near the TSS (Fig. 4a). These profiles of active modifications were common among PS/RS active genes, PS active genes, and constitutively active genes, suggesting that PS-specific gene activation is regulated by a similar epigenetic mechanism with that of constitutively active genes in PS (Fig. 4b, Additional file 1: Figure S4). On the other hand, genes inactivated in PS such as vimentin (Vim) exhibited a distinct feature compared to the constitutively inactive genes: H3K4me2 largely remained in PS at PS/RS inactive genes and PS inactive genes although RNAPII and H3K4me3 were largely depleted (Fig. 4a,c). In addition, the silent modification H3K27me3, but not H3K9me2, was highly enriched at PS/RS inactive genes (Fig. 4a,e). These results suggest that bivalent chromatin signatures such as H3K27me3 with H3K4me2 are associated with PS/RS inactive genes in PS.Fig. 4


Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline.

Sin HS, Kartashov AV, Hasegawa K, Barski A, Namekawa SH - BMC Biol. (2015)

Active marks remain after the inactivation of autosomal somatic/progenitor genes in PS. a Distribution of histone marks around PS/RS inactive Vim gene locus and PS active Sycp3 gene locus in PS. b ATD of active marks at the active genes in PS. c ATD of active marks at the silent genes in PS. d ATD of active marks in PS. These genes are activated in RS. e ATD of each silent mark in representative groups in PS. ATD, average tag density; PS, pachytene spermatocytes; RS, round spermatids
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4508805&req=5

Fig4: Active marks remain after the inactivation of autosomal somatic/progenitor genes in PS. a Distribution of histone marks around PS/RS inactive Vim gene locus and PS active Sycp3 gene locus in PS. b ATD of active marks at the active genes in PS. c ATD of active marks at the silent genes in PS. d ATD of active marks in PS. These genes are activated in RS. e ATD of each silent mark in representative groups in PS. ATD, average tag density; PS, pachytene spermatocytes; RS, round spermatids
Mentions: Next, we sought to examine how the meiosis-specific transcriptome is regulated for autosomes during the PS stage. At the PS active gene synaptonemal complex protein 3 (Sycp3), active modifications such as H3K4me3, H4K8ac, H4K16ac, and Kcr were highly accumulated at the TSS, and H3K4me2 exhibited a broader peak of enrichment near the TSS (Fig. 4a). These profiles of active modifications were common among PS/RS active genes, PS active genes, and constitutively active genes, suggesting that PS-specific gene activation is regulated by a similar epigenetic mechanism with that of constitutively active genes in PS (Fig. 4b, Additional file 1: Figure S4). On the other hand, genes inactivated in PS such as vimentin (Vim) exhibited a distinct feature compared to the constitutively inactive genes: H3K4me2 largely remained in PS at PS/RS inactive genes and PS inactive genes although RNAPII and H3K4me3 were largely depleted (Fig. 4a,c). In addition, the silent modification H3K27me3, but not H3K9me2, was highly enriched at PS/RS inactive genes (Fig. 4a,e). These results suggest that bivalent chromatin signatures such as H3K27me3 with H3K4me2 are associated with PS/RS inactive genes in PS.Fig. 4

Bottom Line: Induction of late spermatogenesis genes during spermatogenesis is facilitated by poised chromatin established in the stem cell phases of spermatogonia, whereas silencing of somatic/progenitor genes during meiosis and postmeiosis is associated with formation of bivalent domains which also allows the recovery of the somatic/progenitor program after fertilization.Importantly, during spermatogenesis mechanisms of epigenetic regulation on sex chromosomes are different from autosomes: X-linked somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation without deposition of H3K27me3.Our results suggest that bivalent H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which maintain bivalent domains that are silent throughout the reproductive cycle), but also underlie reversible silencing of somatic/progenitor genes during the mitosis-to-meiosis transition in late spermatogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

ABSTRACT

Background: The male germline transcriptome changes dramatically during the mitosis-to-meiosis transition to activate late spermatogenesis genes and to transiently suppress genes commonly expressed in somatic lineages and spermatogenesis progenitor cells, termed somatic/progenitor genes.

Results: These changes reflect epigenetic regulation. Induction of late spermatogenesis genes during spermatogenesis is facilitated by poised chromatin established in the stem cell phases of spermatogonia, whereas silencing of somatic/progenitor genes during meiosis and postmeiosis is associated with formation of bivalent domains which also allows the recovery of the somatic/progenitor program after fertilization. Importantly, during spermatogenesis mechanisms of epigenetic regulation on sex chromosomes are different from autosomes: X-linked somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation without deposition of H3K27me3.

Conclusions: Our results suggest that bivalent H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which maintain bivalent domains that are silent throughout the reproductive cycle), but also underlie reversible silencing of somatic/progenitor genes during the mitosis-to-meiosis transition in late spermatogenesis.

No MeSH data available.