Genomics

Dataset Information

149

PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation [ChIP-seq]


ABSTRACT: Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology. Overall design: Genome-wide binding profiles for the co-activator p300 and various histone modifications were investigated in mouse embryonic stem cells (mESC) and AntNPC (anterior neural progenitors).

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Milos Nikolic  

PROVIDER: GSE89209 | GEO | 2017-02-11

SECONDARY ACCESSION(S): PRJNA350689

REPOSITORIES: GEO

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Publications

PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.

Cruz-Molina Sara S   Respuela Patricia P   Tebartz Christina C   Kolovos Petros P   Nikolic Milos M   Fueyo Raquel R   van Ijcken Wilfred F J WFJ   Grosveld Frank F   Frommolt Peter P   Bazzi Hisham H   Rada-Iglesias Alvaro A  

Cell stem cell 20170309 5


Poised enhancers marked by H3K27me3 in pluripotent stem cells have been implicated in the establishment of somatic expression programs during embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Using CRISPR/Cas9 technology to engineer precise genetic deletions, we demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Interestingly, circularized chromosome conforma  ...[more]

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