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Specificity, propagation and memory of pericentric heterochromatin in mouse fibroblasts: H3S10p

ABSTRACT: ChIP-seq of H3S10p in synchronized and asynchronous ESCs and RNA-seq of ESCs after inhibition of AURKB

ORGANISM(S): Mus musculus

PROVIDER: GSE67133 | GEO | 2015/06/17

SECONDARY ACCESSION(S): PRJNA279025

REPOSITORIES: GEO

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Specificity, propagation and memory of pericentric heterochromatin in mouse fibroblasts: H3S10p

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2015-06-17 | E-GEOD-67133 | biostudies-arrayexpress

Specificity, propagation and memory of pericentric heterochromatin in mouse fibroblasts

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Project description:The cell establishes heritable patterns of active and silenced chromatin via interacting factors that set, remove, and read epigenetic marks. To understand how the underlying networks operate, we have dissected transcriptional silencing in pericentric heterochromatin (PCH) of mouse fibroblasts. We assembled a quantitative map for the abundance and interactions of 16 factors related to PCH in living cells and found that stably bound complexes of the histone methyltransferase SUV39H1/2 demarcate the PCH state. From the experimental data, we developed a predictive mathematical model that explains how chromatin-bound SUV39H1/2 complexes act as nucleation sites and propagate a spatially confined PCH domain with elevated histone H3 lysine 9 trimethylation levels via chromatin dynamics. This "nucleation and looping" mechanism is particularly robust toward transient perturbations and stably maintains the PCH state. These features make it an attractive model for establishing functional epigenetic domains throughout the genome based on the localized immobilization of chromatin-modifying enzymes.

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Genome-wide binding of FOXD3 in mouse ESCs

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IGSF11 is required for pericentric heterochromatin dissociation during meiotic diplotene.

Project description:Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes.

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