Expression and replication timing patterns of wildtype and translocated BCL2 genes

Genomics
Y SunT G Krontiris

Abstract

Translocation of the BCL2 gene from chromosome 18 to chromosome 14 results in constitutive expression of the gene. We have recently demonstrated that the major breakpoint region (mbr) of BCL2, which is implicated in 70% of t(14;18) translocations present in human follicular lymphoma, is a matrix attachment region. Since these regions are implicated in control of both transcription and replication, we wished to determine whether BCL2 translocation was also accompanied by changes in replication timing of the translocated allele. Using both fluorescence in situ hybridization and allele-specific PCR, we have demonstrated that the translocated allele replicates at the G1/S boundary, while the wildtype allele continues to replicate as usual in mid-S phase. These differences are accompanied by allele-specific changes in BCL2 expression. Since the net structural effect of t(14;18) translocations within the mbr is to disrupt the BCL2 MAR and replace it with the IGH MARs located just downstream of each breakpoint, we conclude that MAR exchange is a significant, selectable outcome of these translocations. We propose that subsequent changes of replication and transcriptional patterns for the translocated BCL2 allele result from this exchan...Continue Reading

References

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Citations

Sep 18, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Mary B DailShane C Burgess
Oct 12, 2004·Cancer Genetics and Cytogenetics·Mandana MahmoodiJ Steve Hou
Jun 19, 2013·Cell Host & Microbe·Marina LusicMauro Giacca
May 31, 2003·International Journal of Hematology·Martin J S Dyer
Dec 6, 2003·Pharmacological Reviews·Christoph Handschin, Urs A Meyer
Jul 19, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hongbing WangBurhan I Ghanayem
Jun 8, 2017·International Journal of Molecular Sciences·Britny BlumenfeldItamar Simon
Dec 31, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sean EkinsTatiana Nikolskaya
May 6, 2021·International Journal of Molecular Sciences·Lina-Marie BriuJean-Charles Cadoret
Jun 18, 2002·Current Opinion in Cell Biology·David M Gilbert
Jul 20, 2002·Trends in Biotechnology·Sandrine CaburetAaron Bensimon
Jun 5, 2003·Cancer Genetics and Cytogenetics·Hena R AsharKiran Chada

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