Tyrosine phosphorylation of HoxA10 decreases DNA binding and transcriptional repression during interferon γ-induced differentiation of myeloid leukemia cell lines

Elizabeth A. Eklund*, Annika Jalava, Renu Kakar

*Corresponding author for this work

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

The DNA binding affinity of HoxA10 is increased by partnering with Pbx proteins. A consensus sequence for Pbx1-HoxA10 DNA binding has been derived, but genuine target genes have not been identified. We noted that the derived Pbx-HoxA10 DNA-binding consensus is similar to a repressor element in the CYBB promoter. The CYBB gene, which encodes the respiratory burst oxidase component gp91(phox), is expressed only in myeloid cells that have differentiated beyond the promyelocyte stage. In these studies, we demonstrate that interferon γ (IFNγ)-induced differentiation of myeloid cell lines abolishes in vitro Pbx-HoxA10 binding to either the derived consensus or the similar CYBB sequence. We also demonstrate that HoxA10, overexpressed in myeloid cell lines, represses reporter gene expression from artificial promoter constructs with Pbx-HoxA10 binding sites. We determine that HoxA10 has endogenous repression domains that are not functionally altered by IFN-γ treatment. However, IFN-γ-induced differentiation of myeloid cell lines leads to HoxA10 tyrosine phosphorylation, which decreases in vitro DNA binding to PbxHoxA10 binding sites. Therefore, these investigations identify the CYBB gene as a potential target for HoxA10 and define repression of genes expressed in mature myeloid cells as a novel role for HoxA10 during myeloid differentiation.

Original languageEnglish (US)
Pages (from-to)20117-20126
Number of pages10
JournalJournal of Biological Chemistry
Volume275
Issue number26
DOIs
StatePublished - Jun 30 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Tyrosine phosphorylation of HoxA10 decreases DNA binding and transcriptional repression during interferon γ-induced differentiation of myeloid leukemia cell lines'. Together they form a unique fingerprint.

  • Cite this