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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Chromatin immunoprecipitation of Oct4, Nanog and Suz12 in human and mouse embryonic stem cells to identify promoters for miRNAs

ABSTRACT: Understanding the transcriptional regulatory circuitry responsible for pluripotency and self-renewal in embryonic stem (ES) cells is fundamental to understanding human development and realizing the therapeutic potential of these cells. The transcription factor Oct4 and the chromatin-modifying Polycomb complex, key regulators of ES cell pluripotency and self-renewal, contribute to positive and negative control of a known set of protein-coding genes. MicroRNAs (miRNAs), non-coding transcripts that participate in post-transcriptional gene regulation are also important for normal pluripotency and self-renewal in ES cells, but there has been no systematic investigation of how miRNA expression is controlled by transcriptional regulators of ES cell identity. Here we identify promoters for miRNAs in the human and mouse genomes and describe the subset of these genes that are under the control of Oct4 and Polycomb in ES cells. We find that the majority of miRNAs that are uniquely or preferentially expressed in ES cells are bound by and dependent on Oct4. Oct4 also occupies a set of miRNA genes that are co-occupied by the Polycomb Group protein, Suz12. These miRNAs, repressed in ES cells, are later expressed in differentiated cells in a highly tissue-specific fashion, suggesting that they may contribute to cell-fate determinations. These data reveal how the core transcriptional regulatory circuitry of ES cells controls the miRNA expression program that contributes to pluripotency and self-renewal.

ORGANISM(S): Homo sapiens

SUBMITTER: Elizabeth Herbolsheimer

PROVIDER: E-TABM-365 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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