HoxA1O Represses Gene Transcription in Undifferentiated Myeloid Cells by Interaction with Histone Deacetylase 2

Yu Feng Lu, Inna Goldenberg, Ling Bei, Jelena Andrejic, Elizabeth A. Eklund*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The homeodomain proteins, HoxA10 and Pbx1a, interact with negative cis elements to repress gene transcription in undifferentiated myeloid cells. The CYBB and NCF2 genes, which encode the gp91PHOX and p67 PHOX proteins, are two such HoxA10-Pbx1a target genes. In previous studies, we found that HoxA1O-Pbx1a represses transcription of these genes by two mechanisms: competition for DNA binding with transcriptional activators and endogenous repression activity. In these studies, we identify a novel molecular mechanism of endogenous transcriptional repression by HoxA10-Pbx1a. Endogenous repression activity of other Hox-Pbx1a complexes requires recruitment of transcriptional co-repressor proteins by Pbx1a. In contrast, our investigations have determined that HoxA10 has Pbx1a-independent endogenous repression activity. We find that this transcriptional repression activity is abrogated by histone deacetylase inhibitors, suggesting involvement of co-repressor proteins. Consistent with this, we identify HoxA10 amino acids 224-249 as a Pbx1-independent repression domain, which interacts with histone deacetylase 2. We have determined that this HoxA10 domain is not conserved with other Abd Hox proteins, although homology exists with other transcription factors and co-repressors. Understanding the roles different Hox proteins play in myeloid differentiation is a challenging problem. Our results suggest that insight into this problem can be obtained from biochemical characterization of the various molecular mechanisms of Hox protein function.

Original languageEnglish (US)
Pages (from-to)47792-47802
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number48
DOIs
StatePublished - Nov 28 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'HoxA1O Represses Gene Transcription in Undifferentiated Myeloid Cells by Interaction with Histone Deacetylase 2'. Together they form a unique fingerprint.

Cite this