Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation

Marcela Stuardo, Milka Martinez, Karla Hidalgo, Martin Montecino, Amjad Javed, Jane B. Lian, Gary S. Stein, Janet L. Stein, Soraya E. Gutiérrez

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)343-349
Number of pages7
JournalJournal of Cellular Physiology
Volume218
Issue number2
DOIs
Publication statusPublished - Feb 2009

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    Stuardo, M., Martinez, M., Hidalgo, K., Montecino, M., Javed, A., Lian, J. B., Stein, G. S., Stein, J. L., & Gutiérrez, S. E. (2009). Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation. Journal of Cellular Physiology, 218(2), 343-349. https://doi.org/10.1002/jcp.21599