Myc dynamically and preferentially relocates to a transcription factory occupied by Igh.
Transcription in mammalian nuclei is highly compartmentalized in RNA polymerase II-enriched nuclear foci known as transcription factories. Genes in cis and trans can share the same factory, suggesting that genes migrate to preassembled transcription sites. We used fluorescent in situ hybridization to investigate the dynamics of gene association with transcription factories during immediate early (IE) gene induction in mouse B lymphocytes. Here, we show that induction involves rapid gene relocation to transcription factories. Importantly, we find that the Myc proto-oncogene on Chromosome 15 is preferentially recruited to the same transcription factory as the highly transcribed Igh gene located on Chromosome 12. Myc and Igh are the most frequent translocation partners in plasmacytoma and Burkitt lymphoma. Our results show that transcriptional activation of IE genes involves rapid relocation to preassembled transcription factories. Furthermore, the data imply a direct link between the nonrandom interchromosomal organization of transcribed genes at transcription factories and the incidence of specific chromosomal translocations.
Osborne
Cameron S
CS
Laboratory of Chromatin and Gene Expression, The Babraham Institute, Cambridge, United Kingdom. cameron.osborne@bbsrc.ac.uk
Chakalova
Lyubomira
L
Mitchell
Jennifer A
JA
Horton
Alice
A
Wood
Andrew L
AL
Bolland
Daniel J
DJ
Corcoran
Anne E
AE
Fraser
Peter
P
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D050438:Genes, Immunoglobulin Heavy Chain; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D016271:Proto-Oncogene Proteins c-myc; D012319:RNA Polymerase II