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Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE121405 | GEO | 2019/04/18

REPOSITORIES: GEO

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Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [bisulfite-seq]

Project description:Early mammalian development is accompanied by a profound global remodeling of chromatin-based regulation. The Zdbf2 locus provides a valuable model to uncover the effect of dynamic chromatin transition, as it is polycomb silenced in embryonic stem cells (ESCs) and only becomes activated after Long isoform of Zdbf2 (Liz) transcription-dependent de novo DNA methylation during differentiation. Here we show that four enhancers contribute to the Liz-to-Zdbf2 promoter switch, concomitantly with dynamic changes in chromatin architecture. CTCF plays a key role in partitioning the locus in ESCs, when Liz is active and Zdbf2 is silenced. The partition is relieved when Zdbf2 becomes DNA methylated and active. Mutant ESCs that lack the partition fail to properly activate Zdbf2. Notably, the CTCF-based regulation occurs independently of the polycomb and DNA methylation pathways, suggesting a multi-layered regulatory framework that ensures proper epigenetic programming of a developmentally important gene.

2019-04-18 | GSE121402 | GEO

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [ATAC-Seq]

2019-04-18 | GSE121400 | GEO

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [4C-Seq]

2019-04-18 | GSE121399 | GEO

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [RNA-Seq]

2019-04-18 | GSE121403 | GEO

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming

Project description:Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming

| PRJNA497263 | ENA

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [4C-Seq]

Project description:Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [4C-Seq]

| PRJNA497265 | ENA

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [bisulfite-seq]

Project description:Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [bisulfite-seq]

| PRJNA497266 | ENA

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [RNA-Seq]

Project description:Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [RNA-Seq]

| PRJNA497268 | ENA

Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [ATAC-Seq]

Project description:Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming [ATAC-Seq]

| PRJNA497267 | ENA

Dynamic enhancer partitioning instructs activation of a growth-related gene during exit from naive pluripotency.

Project description:During early mammalian development, the chromatin landscape undergoes profound transitions. The Zdbf2 gene-involved in growth control-provides a valuable model to study this window: upon exit from naïve pluripotency and prior to tissue differentiation, it undergoes a switch from a distal to a proximal promoter usage, accompanied by a switch from polycomb to DNA methylation occupancy. Using a mouse embryonic stem cell (ESC) system to mimic this period, we show here that four enhancers contribute to the Zdbf2 promoter switch, concomitantly with dynamic changes in chromatin architecture. In ESCs, the locus is partitioned to facilitate enhancer contacts with the distal Zdbf2 promoter. Relieving the partition enhances proximal Zdbf2 promoter activity, as observed during differentiation or with genetic mutants. Importantly, we show that 3D regulation occurs upstream of the polycomb and DNA methylation pathways. Our study reveals the importance of multi-layered regulatory frameworks to ensure proper spatio-temporal activation of developmentally important genes.

| S-EPMC6488298 | biostudies-literature

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