期刊
EMBO MOLECULAR MEDICINE
卷 2, 期 5, 页码 159-171出版社
WILEY
DOI: 10.1002/emmm.201000067
关键词
B cell lymphoma; GMCL1; heterochromatic foci; nuclear architecture; 1q12 pericentric heterochromatin
资金
- Fondation de France
- Institut National du Cancer
- Association pour la Recherche sur le Cancer
- Region Rhone-Alpes
- canceropole CLARA (EpiMed)
- Ligue Nationale Contre le Cancer (LNCC)-Comites de l'Isere/Savoie
- Delegation Regionale de la Recherche Clinique-CHU de Grenoble
- French GOELAMS clinical trials group
- ARAMIS association
- Ministere de l'Enseignement Superieur et de la Recherche
- Association pour la Recherche sur le Cancer (ARC)
- Societe Francaise d'Hematologie (SFH)
- ARC-ARECA network
- LNCC
Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here, we report the first evidence that a distinct category of chromosomal translocations observed in human tumours-those targeting 1q12 satellite DNA-can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localized to the nuclear periphery and to arise as a consequence of long range 'pairing' between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localization and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in diffuse large B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression via long range epigenetic mechanisms.
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