Histone Methylases MLL1 and MLL3 Coordinate With Estrogen Receptors in Estrogen-Mediated HOXB9 Expression

Biochemistry. 2011 May 3;50(17):3517-27. doi: 10.1021/bi102037t. Epub 2011 Apr 5.

Abstract

Homeobox gene HOXB9 is a critical player in development of mammary gland and sternum and in regulation of renin which is closely linked with blood pressure control. Our studies demonstrated that HOXB9 gene is transcriptionally regulated by estrogen (E2). HOXB9 promoter contains several estrogen-response elements (ERE). Reporter assay based experiments demonstrated that HOXB9 promoter EREs are estrogen responsive. Estrogen receptors ERα and ERβ are essential for E2-mediated transcriptional activation of HOXB9. Chromatin immunoprecipitation assay demonstrated that ERs bind to HOXB9 EREs as a function of E2. Similarly, histone methylases MLL1 and MLL3 also bind to HOXB9 EREs and play a critical role in E2-mediated transcriptional activation of HOXB9. Overall, our studies demonstrated that HOXB9 is an E2-responsive gene and ERs coordinate with MLL1 and MLL3 in E2-mediated transcriptional regulation of HOXB9.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Estradiol / pharmacology*
  • Estrogen Receptor alpha / metabolism*
  • Estrogen Receptor beta / metabolism*
  • Estrogens / pharmacology*
  • Gene Knockdown Techniques
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Transport
  • Transcriptional Activation

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • HOXB9 protein, human
  • Homeodomain Proteins
  • Estradiol
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase