Source:http://linkedlifedata.com/resource/pubmed/id/18853425
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2008-12-1
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pubmed:abstractText |
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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1097-4652
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pubmed:author | |
pubmed:copyrightInfo |
(c) 2008 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
218
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
343-9
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pubmed:meshHeading |
pubmed-meshheading:18853425-Acetylation,
pubmed-meshheading:18853425-Chromatin,
pubmed-meshheading:18853425-Chromosome Breakage,
pubmed-meshheading:18853425-Chromosomes, Human, Pair 21,
pubmed-meshheading:18853425-Chromosomes, Human, Pair 8,
pubmed-meshheading:18853425-Core Binding Factor Alpha 2 Subunit,
pubmed-meshheading:18853425-HL-60 Cells,
pubmed-meshheading:18853425-HeLa Cells,
pubmed-meshheading:18853425-Histones,
pubmed-meshheading:18853425-Humans,
pubmed-meshheading:18853425-Introns,
pubmed-meshheading:18853425-Protein Binding,
pubmed-meshheading:18853425-Translocation, Genetic
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pubmed:year |
2009
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pubmed:articleTitle |
Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation.
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pubmed:affiliation |
Departamento de Bioquímica y Biología Molecular, Universidad de Concepción, Concepción, Chile.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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