title: Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells.
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.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Marson
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Levine
authors.forename: Megan F
authors.initials: MF
authors.lastname: Cole
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Frampton
authors.forename: Tobias
authors.initials: T
authors.lastname: Brambrink
authors.forename: Sarah
authors.initials: S
authors.lastname: Johnstone
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Guenther
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Johnston
authors.forename: Marius
authors.initials: M
authors.lastname: Wernig
authors.forename: Jamie
authors.initials: J
authors.lastname: Newman
authors.forename: J Mauro
authors.initials: JM
authors.lastname: Calabrese
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Dennis
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Volkert
authors.forename: Sumeet
authors.initials: S
authors.lastname: Gupta
authors.forename: Jennifer
authors.initials: J
authors.lastname: Love
authors.forename: Nancy
authors.initials: N
authors.lastname: Hannett
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors