Interaction in vivo between the two matrix attachment regions flanking a single chromatin loop.
In interphase nuclei as in metaphase chromosomes, the genome is organized into topologically closed loop domains. Here, we have mapped the ends of the loop domain that contains the Ifng (interferon-gamma) gene in primary and cultured murine T-lymphocytes. To determine whether the ends of the loop are located in close proximity to each other in the nuclear space, the 3C (chromosome conformation capture) technique, which detects protein-mediated DNA-DNA interactions, was utilized. A strong interaction was demonstrated between the two ends of the loop, which were close enough to become cross-linked in vivo in the presence of paraformaldehyde. Chromatin immunoprecipitation combined with the 3C technique demonstrated that topoisomerase IIalpha and MeCP2, but not topoisomerase IIbeta, heterochromatin-associated protein HP1 or CTCF, were involved in this interaction. The present findings have important implications in terms of mechanisms of illegitimate recombination that can result in chromosomal translocations and deletions.
Eivazova
Elvira R
ER
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN37232, USA.
Gavrilov
Aleksey
A
Pirozhkova
Iryna
I
Petrov
Andrei
A
Iarovaia
Olga V
OV
Razin
Sergey V
SV
Lipinski
Marc
M
Vassetzky
Yegor S
YS
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016678:Genome; D007371:Interferon-gamma / Q000235:genetics; D045170:Matrix Attachment Regions; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D011485:Protein Binding / Q000187:drug effects; D011995:Recombination, Genetic / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D000951:Antigens, Neoplasm; D002843:Chromatin; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D007371:Interferon-gamma; D004250:DNA Topoisomerases, Type II