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Expression data from REST knock-out versus REST wild type cells during in vitro neurogenesis

ABSTRACT: While changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. We developed a computational model on the premise that transcription factors (TFs) direct dynamic chromatin changes during cell fate decisions. When applied to a neurogenesis paradigm, this approach predicted the TF REST as a determinant of gain of Polycomb-mediated H3K27me3 in neuronal progenitor cells. We prove this prediction experimentally by showing that the absence of REST causes loss of H3K27me3 at target promoters in trans at the same cellular state. Moreover, promoter fragments containing a REST binding site are sufficient to recruit H3K27me3 in cis, while deletion of their REST site results in loss of H3K27me3. These findings illustrate that computational modeling can systematically identify TFs that regulate chromatin dynamics genome-wide. Local determination of Polycomb activity by REST exemplifies such TF based regulation of chromatin. Expression profiling of REST knock-out (RESTko) versus REST wildtype (RESTwt) or REST heterozygous knock-out (RESThet) cells at three stages of in vitro neuronal differentiation. RESTko and RESTwt/RESThet embryonic stem (ES) cells were differentiated to terminal neurons (TN) via a defined neuronal progenitor (NP) state. Three biological replicates (suffixes a to c).

ORGANISM(S): Mus musculus

SUBMITTER: Dirk Schuebeler

PROVIDER: E-GEOD-27114 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Role of REST during neuronal differentiation

Project description:This SuperSeries is composed of the following subset Series: GSE27114: Expression data from REST knock-out versus REST wild type cells during in vitro neurogenesis GSE27148: A comparative epigenomics approach reveals REST as a mediator of Polycomb reprogramming during neuronal differentiation Refer to individual Series

2012-09-04 | E-GEOD-27341 | biostudies-arrayexpress

A comparative epigenomics approach reveals REST as a mediator of Polycomb reprogramming during neuronal differentiation

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2011-06-21 | E-GEOD-27827 | biostudies-arrayexpress

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Chromatin based modeling of transcription rates identifies the contribution of different regulatory layers to steady-state mRNA levels.

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