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Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells.

Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Research Abstract Details 

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  • Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Abstract Text:

    jian xuJian Xu,scott d popeScott D Pope,ali r jazirehiAli R Jazirehi,joanne l attemaJoanne L Attema,peter papathanasiouPeter Papathanasiou,jason a wattsJason A Watts,kenneth s zaretKenneth S Zaret,irving l weissmanIrving L Weissman,stephen t smaleStephen T Smale,

    Recent studies have suggested that, in ES cells, inactive genes encoding early developmental regulators possess bivalent histone modification domains and are therefore poised for activation. However, bivalent domains were not observed at typical tissue-specific genes. Here, we show that windows of unmethylated CpG dinucleotides and putative pioneer factor interactions mark enhancers for at least some tissue-specific genes in ES cells. The unmethylated windows expand in cells that express the gene and contract, disappear, or remain unchanged in nonexpressing tissues. However, in ES cells, they do not always coincide with common histone modifications. Genomic footprinting and chromatin immunoprecipitation demonstrated that transcription factor binding underlies the unmethylated windows at enhancers for the Ptcra and Alb1 genes. After stable integration of premethylated Ptcra enhancer constructs into the ES cell genome, the unmethylated windows readily appeared. In contrast, the premethylated constructs remained fully methylated and silent after introduction into Ptcra-expressing thymocytes. These findings provide initial functional support for a model in which pioneer factor interactions in ES cells promote the assembly of a chromatin structure that is permissive for subsequent activation, and in which differentiated tissues lack the machinery required for gene activation when these ES cell marks are absent. The enhancer marks may therefore represent important features of the pluripotent state.

    Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Publishing Authors By Initials

    j xuJ Xu,sd popeSD Pope,ar jazirehiAR Jazirehi,jl attemaJL Attema,p papathanasiouP Papathanasiou,ja wattsJA Watts,ks zaretKS Zaret,il weissmanIL Weissman,st smaleST Smale,

    For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

    PUBMED ID PMID:

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    Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Proceedings of the National Academy of Sciences of

    VOLUME: 104

    Page Numbers: 12377-82

    Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

    ISSN: 0027-8424

    DAY: 18

    MONTH: 07

    YEAR: 2007

    Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7505876

    Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Keywords Mesh Terms:

    KEYWORDS: Transcription, Genetic

    MESH TERMS: genetics

    Chemical & Substance for Abstract: Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Information

    Substance Name: Interleukin-12

    Registry Number: 187348-17-0

    Grant and Affiliation Information for Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells.

    AFFILIATION: Howard Hughes Medical Institute, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIAID

    GRANT: T32 AI07323

    ACRONYM: AI

    MEDLINETA: Proc Natl Acad Sci U S A

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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