T(8;21)(q22;q22) fusion proteins preferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate gene expression

Akiko J. Okumura, Luke F. Peterson, Fumihiko Okumura, Anita Boyapati, Dong Er Zhang

研究成果: ジャーナルへの寄稿学術誌査読

43 被引用数 (Scopus)

抄録

Chromosome abnormalities are frequently associated with cancer development. The 8:21(q22;q22) chromosomal translocation is one of the most common chromosome abnormalities identified in leukemia. It generates fusion proteins between AML1 and ETO. Since AML1 is a well-defined DNA-binding protein, AML1-ETO fusion proteins have been recognized as DNA-binding proteins interacting with the same consensus DNA-binding site as AML1. The alteration of AML1 target gene expression due to the presence of AML1- ETO is related to the development of leukemia. Here, using a 25-bp random double-stranded oligonucleotide library and a polymerase chain reaction (PCR)- based DNA-binding site screen, we show that compared with native AML1. AML1- ETO fusion proteins preferentially bind to DNA sequences with duplicated AML1 consensus sites. This finding is further confirmed by both in vitro and in vivo DNA-protein interaction assays. These results suggest that AML1-ETO fusion proteins have a selective preference for certain AML1 target genes that contain multimerized AML1 consensus sites in their regulatory elements. Such selected regulation provides an important molecular mechanism for the dysregulation of gene expression during cancer development.

本文言語英語
ページ(範囲)1392-1401
ページ数10
ジャーナルBlood
112
4
DOI
出版ステータス出版済み - 8月 15 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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