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西亚试剂：Connecting microRNA Genes to the Core Transcriptional Regul

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

Alexander Marson,1,2,5 Stuart S. Levine,1,5 Megan F. Cole,1,2 Garrett M. Frampton,1,2 Tobias Brambrink,1 Sarah Johnstone,1,2 Matthew G. Guenther,1 Wendy K. Johnston,1,3 Marius Wernig,1 Jamie Newman,1,2 J. Mauro Calabrese,2,4 Lucas M. Dennis,1,2 Thomas L. Volkert,1 Sumeet Gupta,1 Jennifer Love,1 Nancy Hannett,1 Phillip A. Sharp,2,4 David P. Bartel,1,2,3 Rudolf Jaenisch,1,2 and Richard A. Young1,2,

1 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
3 Howard Hughes Medical Institute, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
4 Koch Institute, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA

Corresponding author
Richard A. Young
Summary

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.