Document Detail


Chromatin signature of embryonic pluripotency is established during genome activation.
MedLine Citation:
PMID:  20336069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
After fertilization the embryonic genome is inactive until transcription is initiated during the maternal-zygotic transition. This transition coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem cells. To study the changes in chromatin structure that accompany pluripotency and genome activation, we mapped the genomic locations of histone H3 molecules bearing lysine trimethylation modifications before and after the maternal-zygotic transition in zebrafish. Histone H3 lysine 27 trimethylation (H3K27me3), which is repressive, and H3K4me3, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by H3K4me3, including many inactive developmental regulatory genes that were also marked by H3K27me3. Sequential chromatin immunoprecipitation demonstrated that the same promoter regions had both trimethylation marks. Such bivalent chromatin domains also exist in embryonic stem cells and are thought to poise genes for activation while keeping them repressed. Furthermore, we found many inactive genes that were uniquely marked by H3K4me3. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published data sets revealed similar monovalent domains in embryonic stem cells. Moreover, H3K4me3 marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA polymerase II, as indicated by the analysis of an inducible transgene. These results indicate that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during the maternal-zygotic transition.
Authors:
Nadine L Vastenhouw; Yong Zhang; Ian G Woods; Farhad Imam; Aviv Regev; X Shirley Liu; John Rinn; Alexander F Schier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-24
Journal Detail:
Title:  Nature     Volume:  464     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-08     Completed Date:  2010-05-17     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  922-6     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GPL9970;  GSE20023
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromatin / genetics*,  metabolism*
Chromatin Immunoprecipitation
Gene Expression Regulation, Developmental* / genetics
Gene Silencing
Genome / genetics*
Histones / chemistry,  metabolism
Lysine / metabolism
Methylation
Oligonucleotide Array Sequence Analysis
Pluripotent Stem Cells / metabolism*
Promoter Regions, Genetic / genetics
RNA Polymerase II / metabolism
Transcriptional Activation
Transgenes
Zebrafish / embryology*,  genetics*,  metabolism
Zebrafish Proteins / genetics
Zygote / cytology,  metabolism
Grant Support
ID/Acronym/Agency:
1R01 HG004069/HG/NHGRI NIH HHS; 5R01 GM56211/GM/NIGMS NIH HHS; DP1 OD003958-05/OD/NIH HHS; R01 GM056211-11/GM/NIGMS NIH HHS; R01 GM056211-12/GM/NIGMS NIH HHS; R01 GM056211-12S1/GM/NIGMS NIH HHS; R01 GM056211-13/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Chromatin; 0/Histones; 0/Zebrafish Proteins; 56-87-1/Lysine; EC 2.7.7.-/RNA Polymerase II
Comments/Corrections

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