Altered chromatin modifications inAML1/RUNX1breakpoint regions involved in (8;21) translocation
| Autor: | Soraya E. Gutierrez, Jane B. Lian, Gary S. Stein, Marcela Stuardo, Karla Hidalgo, Amjad Javed, Martin Montecino, Milka Martinez, Janet L. Stein |
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| Rok vydání: | 2009 |
| Předmět: |
Chromosomes
Human Pair 21 Physiology Clinical Biochemistry HL-60 Cells Chromosomal translocation Biology Translocation Genetic Histones chemistry.chemical_compound Histone H3 Histone H1 hemic and lymphatic diseases Histone H2A Humans ChIA-PET Acetylation Chromosome Breakage Cell Biology Molecular biology Chromatin Introns RUNX1 chemistry Core Binding Factor Alpha 2 Subunit Chromatin immunoprecipitation Chromosomes Human Pair 8 HeLa Cells Protein Binding |
| Zdroj: | JOURNAL OF CELLULAR PHYSIOLOGY Artículos CONICYT CONICYT Chile instacron:CONICYT |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | 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. J. Cell. Physiol. 218: 343–349, 2009. © 2008 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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