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Cell type-specific DNA methylation patterns in the human breast.

Cell type-specific DNA methylation patterns in the human breast. Research Abstract Details 

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  • Cell type-specific DNA methylation patterns in the human breast. Abstract Text:

    Cellular identity and differentiation are determined by epigenetic programs. The characteristics of these programs in normal human mammary epithelium and their similarity to those in stem cells are unknown. To begin investigating these issues, we analyzed the DNA methylation and gene expression profiles of distinct subpopulations of mammary epithelial cells by using MSDK (methylation-specific digital karyotyping) and SAGE (serial analysis of gene expression). We identified discrete cell-type and differentiation state-specific DNA methylation and gene expression patterns that were maintained in a subset of breast carcinomas and correlated with clinically relevant tumor subtypes. CD44+ cells were the most hypomethylated and highly expressed several transcription factors with known stem cell function including HOXA10 and TCF3. Many of these genes were also hypomethylated in BMP4-treated compared with undifferentiated human embryonic stem (ES) cells that we analyzed by MSDK for comparison. Further highlighting the similarity of epigenetic programs of embryonic and mammary epithelial cells, genes highly expressed in CD44+ relative to more differentiated CD24+ cells were significantly enriched for Suz12 targets in ES cells. The expression of FOXC1, one of the transcription factors hypomethylated and highly expressed in CD44+ cells, induced a progenitor-like phenotype in differentiated mammary epithelial cells. These data suggest that epigenetically controlled transcription factors play a key role in regulating mammary epithelial cell phenotypes and imply similarities among epigenetic programs that define progenitor cell characteristics.

    Cell type-specific DNA methylation patterns in the human breast. Publishing Authors By Initials

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    PUBMED ID PMID:

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    Cell type-specific DNA methylation patterns in the human breast. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Proceedings of the National Academy of Sciences of

    VOLUME: 105

    Page Numbers: 14076-81

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

    ISSN: 1091-6490

    DAY: 9

    MONTH: 09

    YEAR: 2008

    Cell type-specific DNA methylation patterns in the human breast. Information

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    LANGUAGE: eng

    NlmUniqueID: 7505876

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    Grant and Affiliation Information for Cell type-specific DNA methylation patterns in the human breast.

    AFFILIATION: Departments of Medical Oncology and Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Proc Natl Acad Sci U S A

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