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Title: Dynamics of Genomic H3K27me3 Domains and Role of EZH2 during Pancreatic Endocrine Specification      
dateReleased:
07-28-2014
description:
Endoderm cells undergo a sequence of fate choices to generate insulin-secreting β cells. Studies of chromatin transitions during this process have been limited to the pancreatic progenitor stage that can be reconstituted from stem cells in vitro, with a gap in understanding the induction of endocrine cells. To address this, we established conditions for isolating endoderm cells, pancreatic progenitors, and endocrine cells from different staged embryos and performed genome wide analysis of the H3K27me3 mark of the repressive Polycomb complex. During the transition from endoderm to pancreas progenitors and during the transition from pancreas progenitors to endocrine cells, genes that lose the H3K27me3 mark typically encode transcriptional regulators, whereas genes that acquire the mark typically are involved in cell biology morphogenesis. Precocious depletion of the EZH2, a H3K27 methylase, at the pancreas progenitor stage enhanced the production of endocrine cells, leading to a later increase in pancreatic beta cells. Similarly, pharmacologic inhibition of EZH2 in embryonic pancreatic tissue explants and human embryonic stem cell cultures led to an increase in endocrine progenitors in vitro. These findings reveal a repeating target gene pattern in H3K27me3 dynamics and provide a means to modulate β cell development from stem cells. Analyzed five FACS-sorted tissues in early mouse embryo; for each tissue we sequenced H3K27me3 and input; no replicates
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-56617
refinement:
raw
alternateIdentifiers:
56617
keywords:
functional genomics
dateModified:
09-08-2014
availability:
available
types:
gene expression
name:
Mus musculus
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-56617/E-GEOD-56617.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-56617/E-GEOD-56617.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56617
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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