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Kisseljova N.P.,University Paris - Sud | Dmitriev P.,University Paris - Sud | Dmitriev P.,Laboratoire Franco Russe Of Recherche En Oncologie | Dmitriev P.,French Institute of Health and Medical Research | And 18 more authors.
European Journal of Human Genetics | Year: 2014

Mechanisms that regulate attachment of the scaffold/matrix attachment regions (S/MARs) to the nuclear matrix remain largely unknown. We have studied the effect of simple sequence length polymorphism (SSLP), DNA methylation and chromatin organization in an S/MAR implicated in facioscapulohumeral dystrophy (FSHD), a hereditary disease linked to a partial deletion of the D4Z4 repeat array on chromosome 4q. This FSHD-related nuclear matrix attachment region (FR-MAR) loses its efficiency in myoblasts from FSHD patients. Three criteria were found to be important for high-Affinity interaction between the FR-MAR and the nuclear matrix: the presence of a specific SSLP haplotype in chromosomal DNA, the methylation of one specific CpG within the FR-MAR and the absence of histone H3 acetylated on lysine 9 in the relevant chromatin fragment. © 2014 Macmillan Publishers Limited. All rights reserved.

PubMed | Laboratoire Franco Russe Of Recherche En Oncologie, French Institute of Health and Medical Research and University Paris - Sud
Type: Journal Article | Journal: Journal of cellular biochemistry | Year: 2016

The immunoglobulin heavy chain (IGH) locus is submitted to intra-chromosomal DNA breakages and rearrangements during normal B cell differentiation that create a risk for illegitimate inter-chromosomal translocations leading to a variety of B-cell malignancies. In most Burkitts and Mantle Cell lymphomas, specific chromosomal translocations juxtapose the IGH locus with a CMYC or Cyclin D1 (CCND1) gene, respectively. 3D-fluorescence in situ hybridization was performed on normal peripheral B lymphocytes induced to mature in vitro from a naive state to the stage where they undergo somatic hypermutation (SHM) and class switch recombination (CSR). The CCND1 genes were found very close to the IGH locus in naive B cells and further away after maturation. In contrast, the CMYC alleles became localized closer to an IGH locus at the stage of SHM/CSR. The colocalization observed between the two oncogenes and the IGH locus at successive stages of B-cell differentiation occurred in the immediate vicinity of the nucleolus, consistent with the known localization of the RAGs and AID enzymes whose function has been demonstrated in IGH physiological rearrangements. We propose that the chromosomal events leading to Mantle Cell lymphoma and Burkitts lymphoma are favored by the colocalization of CCND1 and CMYC with IGH at the time the concerned B cells undergo VDJ recombination or SHM/CSR, respectively. J. Cell. Biochem. 117: 1506-1510, 2016. 2016 Wiley Periodicals, Inc.

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