AML1A and AML1B Can Transactivate the Human IL-3 Promoter

Hideo Uchida, Jin Zhang, Stephen D. Nimer

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

The AML1 gene encodes several transcription factors, including AML1A and AML1B, which bind to DNA via a TGT/cGGT consensus sequence that is found in several promoters, including the human IL-3 promoter. We performed cotransfection experiments in T cells, and demonstrated that although AML1A lacks a putative transactivation domain, it can transactivate the IL-3 promoter nearly as effectively as AML1B, a known activator. A consensus AML1 binding site (TGTGGT), located in the previously identified DNase I footprint region A of the human IL-3 promoter (extending from bp -165 to -128), and a sequence similar to the consensus binding site (TGTGGG), located in footprint region B (bp -55 to -42), specifically bind AML1 proteins in gel shift assays. The affinity for the TGTGGG sequence was much less than that for the TGTGGT sequence, and mutating the TGTGGG sequence did not alter the IL-3 promoter activity, whereas mutation of the consensus binding site decreased the basal promoter activity and nearly eliminated transactivation by AML1A and AML1B. The AML1/ETO fusion protein, generated by the t(8;21) translocation, repressed IL-3 promoter activity, although the AML1 portion of AML1/ETO (amino acids 1-177) lacked transcriptional regulatory activity and did not bind to DNA in vitro. The 60- to 177-amino acid portion of AML1 readily bound DNA, suggesting that the first 59 amino acids may function as an inhibitory domain for DNA binding. Demonstration of the transactivation by AML1A and localization of a putative inhibitory binding domain suggest additional complexity within this family of transcription factors.

Original languageEnglish (US)
Pages (from-to)2251-2258
Number of pages8
JournalJournal of Immunology
Volume158
Issue number5
StatePublished - Mar 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'AML1A and AML1B Can Transactivate the Human IL-3 Promoter'. Together they form a unique fingerprint.

  • Cite this