Altered Chromatin Modifications in AML1/RUNX1 Breakpoint Regions Involved in (8;21) Translocation

Stuardo, M.; Martínez M; Hidalgo K.; Montecino, M.; Javed, A; Lian, JB; Stein, GS; Stein, JL; Gutierrez, SE

Abstract

The RUNX1/AML1 gene is the most frequent target for chromosomal translocation, and often identified as a site for reciprocal rearrangement of chromosomes 8 and 21 in patients with acute myelogenous leukemia. Virtually all chromosome translocations in leukemia show no consistent homologous sequences at the breakpoint regions. However, specific chromatin elements (DNase I and topoisomerase II cleavage) have been found at the breakpoints of some genes suggesting that structural motifs are determinant for the double strand DNA-breaks. We analyzed the chromatin organization at intron 5 of the RUNX1 gene where all the sequenced breakpoints involved in t(8;21) have been mapped. Using chromatin immunoprecipitation assays we show that chromatin organization at intron 5 of the RUNX1 gene is different in HL-60 and HeLa cells. Two distinct features mark the intron 5 in cells expressing RUNX1: a complete lack or significantly reduced levels of Histone H1 and enrichment of hyperacetylated histone H3. Strikingly, induction of DNA damage resulted in formation of t(8;21) in HL-60 but not in HeLa cells. Taken together, our results suggest that H1 depletion and/or histone H3 hyperacetylation may have a linkage with an increase susceptibility of specific chromosomal regions to undergo translocations. © 2008 Wiley-Liss, Inc.

Más información

Título según WOS: Altered Chromatin Modifications in AML1/RUNX1 Breakpoint Regions Involved in (8;21) Translocation
Título según SCOPUS: Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation
Título de la Revista: JOURNAL OF CELLULAR PHYSIOLOGY
Volumen: 218
Número: 2
Editorial: Wiley
Fecha de publicación: 2009
Página de inicio: 343
Página final: 349
Idioma: English
URL: http://doi.wiley.com/10.1002/jcp.21599
DOI:

10.1002/jcp.21599

Notas: ISI, SCOPUS