Gene expression profiling identifies Hes6 as a transcriptional target of ATOH1 in cochlear hair cells

FEBS Lett. 2007 Oct 2;581(24):4651-6. doi: 10.1016/j.febslet.2007.08.059. Epub 2007 Sep 4.

Abstract

ATOH1 is a basic Helix-Loop-Helix transcription factor crucial for hair cell (HC) differentiation in the inner ear. In order to identify ATOH1 target genes, we performed a genome-wide expression profiling analysis in cells expressing ATOH1 under the control of a tetracycline-off system and found that HES6 expression is induced by ATOH1. We performed in situ hybridisation and showed that the rise and fall of Hes6 expression closely follow that of Atoh1 in cochlear HC. Moreover, electrophoretic mobility shift assays and luciferase assays show that ATOH1 activates HES6 transcription through binding to three clustered E boxes of its promoter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Line, Tumor
  • Conserved Sequence
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Hair Cells, Auditory / metabolism*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Transcription, Genetic / genetics

Substances

  • ATOH1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • HES6 protein, human
  • Hes6 protein, mouse
  • Repressor Proteins