Connecting MicroRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2008 Aug 12

PMID 18692474

Citations 811

Authors

Alexander Marson

Stuart S Levine

Megan F Cole

Garrett M Frampton

Tobias Brambrink

Sarah Johnstone

Matthew G Guenther

Wendy K Johnston

Marius Wernig

Jamie Newman

J Mauro Calabrese

Lucas M Dennis

Thomas L Volkert

Sumeet Gupta

Jennifer Love

Nancy Hannett

Phillip A Sharp

David P Bartel

Rudolf Jaenisch

Richard A Young

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here the transcriptional regulatory circuitry of ES cells that incorporates protein-coding and miRNA genes based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb group proteins in ES cells and shows tissue-specific expression in differentiated cells. These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity.

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