Chromatin structure analyses identify miRNA promoters.
Although microRNAs (miRNAs) are key regulators of gene expression in normal human physiology and disease, transcriptional regulation of miRNAs is poorly understood, because most miRNA promoters have not yet been characterized. We identified the proximal promoters of 175 human miRNAs by combining nucleosome mapping with chromatin signatures for promoters. We observe that one-third of intronic miRNAs have transcription initiation regions independent from their host promoters and present a list of RNA polymerase II- and III-occupied miRNAs. Nucleosome mapping and linker sequence analyses in miRNA promoters permitted accurate prediction of transcription factors regulating miRNA expression, thus identifying nine miRNAs regulated by the MITF transcription factor/oncoprotein in melanoma cells. Furthermore, DNA sequences encoding mature miRNAs were found to be preferentially occupied by positioned-nucleosomes, and the 3' end sites of known genes exhibited nucleosome depletion. The high-throughput identification of miRNA promoter and enhancer regulatory elements sheds light on evolution of miRNA transcription and permits rapid identification of transcriptional networks of miRNAs.
Ozsolak
Fatih
F
Department of Dermatology and Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Poling
Laura L
LL
Wang
Zhengxin
Z
Liu
Hui
H
Liu
X Shirley
XS
Roeder
Robert G
RG
Zhang
Xinmin
X
Song
Jun S
JS
Fisher
David E
DE
D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D002843:Chromatin; D035683:MicroRNAs; D009707:Nucleosomes; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D008156:Luciferases