Acetylation of Ets-1 is the key to chromatin remodeling for miR-192 expression

Research output: Contribution to journalShort survey

8 Citations (Scopus)

Abstract

By regulating gene expression, microRNAs (miRNAs) play pivotal roles in physiological and pathological processes. However, the regulation of miRNAs is elusive. miR-192 is a key regulator of renal fi brosis and hypertrophy in diabetic nephropathy. Natarajan et al. showed that the miR-192 gene contains an upstream region with Ets-1 and Smad3 binding sites. In control cells, all Ets-1 sites were occupied, resulting in a locked chromatin structure that kept miR-192 expression low. In response to transforming growth factor-β (TGF-β) stimulation, Smad3 and Akt were activated, and the latter further activated p300 to induce partial acetylation and dissociation of Ets-1 and the recruitment of Smad3 to the miR-192 gene, inducing transient miR-192 expression. During prolonged TGF-β treatment, p300 acetylated histone and Ets-1, resulting in complete dissociation of Ets-1 and the opening of the chromatin for sustained miR-192 expression. Thus, transcription factors and chromatin remodeling control microRNA gene expression in a dynamic, coordinated fashion.

Original languageEnglish (US)
Article numberpe21
JournalScience Signaling
Volume6
Issue number278
DOIs
StatePublished - Jun 4 2013

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Acetylation
Chromatin Assembly and Disassembly
MicroRNAs
Chromatin
Transforming Growth Factors
Gene expression
Genes
Physiological Phenomena
Gene Expression
Diabetic Nephropathies
Pathologic Processes
Histones
Hypertrophy
Transcription Factors
Binding Sites
Kidney

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Acetylation of Ets-1 is the key to chromatin remodeling for miR-192 expression. / Dong, Zheng.

In: Science Signaling, Vol. 6, No. 278, pe21, 04.06.2013.

Research output: Contribution to journalShort survey

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abstract = "By regulating gene expression, microRNAs (miRNAs) play pivotal roles in physiological and pathological processes. However, the regulation of miRNAs is elusive. miR-192 is a key regulator of renal fi brosis and hypertrophy in diabetic nephropathy. Natarajan et al. showed that the miR-192 gene contains an upstream region with Ets-1 and Smad3 binding sites. In control cells, all Ets-1 sites were occupied, resulting in a locked chromatin structure that kept miR-192 expression low. In response to transforming growth factor-β (TGF-β) stimulation, Smad3 and Akt were activated, and the latter further activated p300 to induce partial acetylation and dissociation of Ets-1 and the recruitment of Smad3 to the miR-192 gene, inducing transient miR-192 expression. During prolonged TGF-β treatment, p300 acetylated histone and Ets-1, resulting in complete dissociation of Ets-1 and the opening of the chromatin for sustained miR-192 expression. Thus, transcription factors and chromatin remodeling control microRNA gene expression in a dynamic, coordinated fashion.",
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