Editors' ChoiceCancer

Gene Silencing in Leukemia?

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Science's STKE  31 Aug 2004:
Vol. 2004, Issue 248, pp. tw310
DOI: 10.1126/stke.2482004tw310

About 15% of acute myeloid leukemia cases display a chromosomal translocation with high-level expression of leukemogenic AML1-ETO fusion proteins. AML1-ETO contains a conserved TAF4-homology domain (TAFH) for which in vivo function is unknown but that might be expected to complex with other transcription factors. Zhang et al. now show that the TAFH domain AML1-ETO, and nonleukemic factor ETO, associates with HEB protein, a transcription factor of the E protein family. The domain by which ETO interacts with E protein coincides with the site targeted by p300/CBP histone acetyltransferase. The association of HEB and ETO may sterically block p300/CBP recruitment in vivo and allow recruitment of negative cofactors, such as HDACs, for gene silencing of HEB-responsive promoters in leukemic cells.

J. Zhang, M. Kalkum, S. Yamamura, B. T. Chait, R. G. Roeder, E protein silencing by the leukemogenic AML1-ETO fusion protein. Science 305, 1286-1289 (2004). [Abstract] [Full Text]

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