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

Fingerprint

Chromatin
Genes
Histones
Introns
Chromosomes
HeLa Cells
Chromosomes, Human, Pair 21
Chromosomes, Human, Pair 8
Type II DNA Topoisomerase
Genetic Translocation
Double-Stranded DNA Breaks
Chromatin Immunoprecipitation
HL-60 Cells
Deoxyribonuclease I
DNA
Sequence Homology
Acute Myeloid Leukemia
DNA Damage
Assays
Leukemia

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Stuardo, Marcela ; Martinez, Milka ; Hidalgo, Karla ; Montecino, Martin ; Javed, Amjad ; Lian, Jane B. ; Stein, Gary S. ; Stein, Janet L. ; Gutiérrez, Soraya E. / Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation. In: Journal of Cellular Physiology. 2009 ; Vol. 218, No. 2. pp. 343-349.
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Stuardo, M, Martinez, M, Hidalgo, K, Montecino, M, Javed, A, Lian, JB, Stein, GS, Stein, JL & Gutiérrez, SE 2009, 'Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation', Journal of Cellular Physiology, vol. 218, no. 2, pp. 343-349. https://doi.org/10.1002/jcp.21599

Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation. / Stuardo, Marcela; Martinez, Milka; Hidalgo, Karla; Montecino, Martin; Javed, Amjad; Lian, Jane B.; Stein, Gary S.; Stein, Janet L.; Gutiérrez, Soraya E.

In: Journal of Cellular Physiology, Vol. 218, No. 2, 02.2009, p. 343-349.

Research output: Contribution to journalArticle

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