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Chromatin Open/Close Logic in Cellular Reprogramming

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

ORGANISM(S): Mus musculus

PROVIDER: GSE93029 | GEO | 2017/12/09

SECONDARY ACCESSION(S): PRJNA359485

REPOSITORIES: GEO

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Chromatin Open/Close Logic in Cellular Reprogramming [ChIP-Seq]

Project description:The reprogramming of fibroblasts into pluripotent stem cells by Oct4, Sox2, Myc and Klf4 represents a unique system to understand the logic of cell fate decisions. The reprogramming process can be divided into initial, middle and maturation phases that are coupled to the ordered execution of multiple biological processes, of which one of the earliest is a mesenchymal to epithelial transition (MET). Yet, despite these critical insights, less is known about how the reprogramming factors alter the chromatin state to convert somatic cells back to pluripotent cells. Here we report the global chromatin accessibility dynamics as cells reprogram from a somatic to a pluripotent state as assessed by assay for transposase-accessible chromatin with sequencing (ATAC-seq). We show that chromatin changes during reprogramming are defined by a fast initial wave of chromatin changes from accessible/open to inaccessible/closed (OC), which is followed by a slower opening up of chromatin from closed to open (CO), and ends with a climactic wave of CO. The initial OC wave includes loci enriched with motifs for AP-1, TEAD, RUNX and ETS-family transcription factors. Consistently, over-expression of one of the AP-1-family members c-Jun, c-Fos and Fra1blocked reprogramming. c-Jun inhibits reprogramming by preventing OSK-driven OC and skewing the overall OC-CO dynamics. Paradoxically, we show that Sox2 and to a less extent Oct4 and Klf4 are CO-, not OC-, mediators , suggesting that they must first activate potent OC factors to remodel chromatin. Indeed, we show that Sap30, a component of the Sin3 complex8, functions as such an OC factor. Together, our results reveal the chromatin accessibility logic during reprogramming and identify Sap30 as one of the first responders that help silence somatic genes.

2017-12-09 | GSE98404 | GEO

Chromatin Open/Close Logic in Cellular Reprogramming [RNA-Seq]

2017-12-09 | GSE93027 | GEO

Chromatin Open/Close Logic in Cellular Reprogramming [ATAC-Seq]

2017-12-09 | GSE93026 | GEO

Chromatin Open/Close Logic in Cellular Reprogramming

Project description:Chromatin Open/Close Logic in Cellular Reprogramming

| PRJNA359485 | ENA

The human cellular nucleic acid binding protien binds G-rich elements close to translation initiation sires and promotes translation.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-01-08 | E-GEOD-76629 | biostudies-arrayexpress

Open chromatin mapping identifies transcriptional networks regulating human epididymis epithelial function