Document Detail


Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2.
MedLine Citation:
PMID:  22902501     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by using the pluripotency factors Oct4, Sox2, Klf4 and c-Myc (together referred to as OSKM). iPSC reprogramming erases somatic epigenetic signatures-as typified by DNA methylation or histone modification at silent pluripotency loci-and establishes alternative epigenetic marks of embryonic stem cells (ESCs). Here we describe an early and essential stage of somatic cell reprogramming, preceding the induction of transcription at endogenous pluripotency loci such as Nanog and Esrrb. By day 4 after transduction with OSKM, two epigenetic modification factors necessary for iPSC generation, namely poly(ADP-ribose) polymerase-1 (Parp1) and ten-eleven translocation-2 (Tet2), are recruited to the Nanog and Esrrb loci. These epigenetic modification factors seem to have complementary roles in the establishment of early epigenetic marks during somatic cell reprogramming: Parp1 functions in the regulation of 5-methylcytosine (5mC) modification, whereas Tet2 is essential for the early generation of 5-hydroxymethylcytosine (5hmC) by the oxidation of 5mC (refs 3,4). Although 5hmC has been proposed to serve primarily as an intermediate in 5mC demethylation to cytosine in certain contexts, our data, and also studies of Tet2-mutant human tumour cells, argue in favour of a role for 5hmC as an epigenetic mark distinct from 5mC. Consistent with this, Parp1 and Tet2 are each needed for the early establishment of histone modifications that typify an activated chromatin state at pluripotency loci, whereas Parp1 induction further promotes accessibility to the Oct4 reprogramming factor. These findings suggest that Parp1 and Tet2 contribute to an epigenetic program that directs subsequent transcriptional induction at pluripotency loci during somatic cell reprogramming.
Authors:
Claudia A Doege; Keiichi Inoue; Toru Yamashita; David B Rhee; Skylar Travis; Ryousuke Fujita; Paolo Guarnieri; Govind Bhagat; William B Vanti; Alan Shih; Ross L Levine; Sara Nik; Emily I Chen; Asa Abeliovich
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-19
Journal Detail:
Title:  Nature     Volume:  -     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Pathology and Cell Biology and Neurology, Taub Institute for Aging, Columbia University, New York, New York 10032, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Dopamine neurons modulate pheromone responses in Drosophila courtship learning.
Next Document:  Rapid induction of inflammatory lipid mediators by the inflammasome in vivo.