Chromatin structure analyses identify miRNA promoters

Fatih Ozsolak, Laura L. Poling, Zhengxin Wang, Hui Liu, X. Shirley Liu, Robert G. Roeder, Xinmin Zhang, Jun S. Song, David E. Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3172-3183
Number of pages12
JournalGenes and Development
Volume22
Issue number22
DOIs
StatePublished - Nov 15 2008
Externally publishedYes

Keywords

  • Chromatin
  • MicroRNA
  • Promoter
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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