ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline.

H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that in male meiosis, ATF7IP2 amasses on autosomal and X-pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X-pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein's essential roles in the maintenance of MSCI, suppression of retrotransposons, and global up-regulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.

ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline.

H3K9 tri-methylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that, in male meiosis, ATF7IP2 amasses on autosomal and X pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein's essential roles in the maintenance of MSCI, suppression of retrotransposons, and global upregulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.

Support for the adaptive decoupling hypothesis from whole-transcriptome profiles of a hypermetamorphic and sexually dimorphic insect, Neodiprion lecontei.

Though seemingly bizarre, the dramatic morphological and ecological transformation that occurs when immature life stages metamorphose into reproductive adults is one of the most successful developmental strategies on the planet. The adaptive decoupling hypothesis (ADH) proposes that metamorphosis is an adaptation for breaking developmental links between traits expressed in different life stages, thereby facilitating their independent evolution when exposed to opposing selection pressures. Here, we draw inspiration from the ADH to develop a conceptual framework for understanding changes in gene expression across ontogeny. We hypothesized that patterns of stage-biased and sex-biased gene expression are the product of both decoupling mechanisms and selection history. To test this hypothesis, we characterized transcriptome-wide patterns of gene-expression traits for three ecologically distinct larval stages (all male) and adult males and females of a hypermetamorphic insect (Neodiprion lecontei). We found that stage-biased gene expression was most pronounced between larval and adult males, which is consistent with the ADH. However, even in the absence of a metamorphic transition, considerable stage-biased expression was observed among morphologically and behaviourally distinct larval stages. Stage-biased expression was also observed across ecologically relevant Gene Ontology categories and genes, highlighting the role of ecology in shaping patterns of gene expression. We also found that the magnitude and prevalence of stage-biased expression far exceeded adult sex-biased expression. Overall, our results highlight how the ADH can shed light on transcriptome-wide patterns of gene expression in organisms with complex life cycles. For maximal insight, detailed knowledge of organismal ecology is also essential.