Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation
Department of Cell Biology
Acetylation; Chromatin; *Chromosome Breakage; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 8; Core Binding Factor Alpha 2 Subunit; HL-60 Cells; Hela Cells; Histones; Humans; Introns; Protein Binding; Translocation, Genetic
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.
DOI of Published Version
J Cell Physiol. 2009 Feb;218(2):343-9. Link to article on publisher's site
Journal of cellular physiology
Stuardo M, Martinez M, Hildago K, Montecino MA, Javed A, Lian JB, Stein GS, Stein JL, Gutierrez SE. (2009). Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation. Stein, Stein, Lian, vanWijnen Lab Publications. https://doi.org/10.1002/jcp.21599. Retrieved from https://escholarship.umassmed.edu/stein/44