Key Points We propose a novel oncogenic mechanism linked to the perinucleolar relocalization of chromosomal segments resulting from the translocation. MCL and BL translocations result in new Ccnd1 and c-myc nuclear positioning, respectively, and nucleolin-dependent activation in both cases.

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.

Individuals infected with human immunodeficiency virus (HIV) are at increased risk for Burkitt lymphoma, a B‐cell malignancy which occurs after a chromosomal translocation rearranging the MYC oncogene with an immunoglobulin gene locus, usually the IGH heavy chain gene locus. We have previously reported that the HIV protein Tat which circulates in all HIV‐positive individuals whatever their immune status caused an increased rate of colocalization between IGH and MYC in B‐cells nuclei. We here present in vitro evidence that Tat activates the expression of the AICDA gene that encodes the activation‐induced cytidine deaminase whose physiological function is to create double‐strand breaks for immunoglobulin gene maturation. In the presence of Tat, DNA damage was observed concomitantly in both MYC and IGH, followed by DNA repair by nonhomologous end joining. AICDA was further found overexpressed in vivo in peripheral blood B‐cells from HIV‐infected individuals. Thus, the capacity of Tat to spontaneously penetrate B‐cells could be sufficient to favor the occurrence of MYC‐IGH oncogenic rearrangements during erroneous repair, a plausible cause for the increased incidence of Burkitt lymphoma in the HIV‐infected population.

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A vast majority of lymphomas and leukaemias are results of translocations. These translocations produce various genetic and epigenetic changes that lead to oncogenesis. This opens an opportunity to use a relatively new class of anti-cancer agents, inhibitors of histone deacetylases (HDACi) to target lymphoid malignancies. Surprisingly, the rational basis for treatment of lymphomas with HDACi is far from clear, although some positive results have been obtained. Here we analyze the effect of histone deacetylase (HDAC) inhibitors on lymphoid malignancies.

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