|Title||Disruption of an imprinted gene cluster by a targeted chromosomal translocation in mice.|
|Publication Type||Journal Article|
|Year of Publication||2001|
|Authors||Cleary, MA, van Raamsdonk, CD, Levorse, J, Zheng, B, Bradley, A, Tilghman, SM|
|Date Published||2001 Sep|
|Keywords||Animals, Base Sequence, Chromosome Mapping, DNA Primers, Genetic Linkage, Genomic Imprinting, In Situ Hybridization, Fluorescence, Mice, Mice, Inbred C57BL, Multigene Family, Translocation, Genetic|
Genomic imprinting is an epigenetic process in which the activity of a gene is determined by its parent of origin. Mechanisms governing genomic imprinting are just beginning to be understood. However, the tendency of imprinted genes to exist in chromosomal clusters suggests a sharing of regulatory elements. To better understand imprinted gene clustering, we disrupted a cluster of imprinted genes on mouse distal chromosome 7 using the Cre/loxP recombination system. In mice carrying a site-specific translocation separating Cdkn1c and Kcnq1, imprinting of the genes retained on chromosome 7, including Kcnq1, Kcnq1ot1, Ascl2, H19 and Igf2, is unaffected, demonstrating that these genes are not regulated by elements near or telomeric to Cdkn1c. In contrast, expression and imprinting of the translocated Cdkn1c, Slc22a1l and Tssc3 on chromosome 11 are affected, consistent with the hypothesis that elements regulating both expression and imprinting of these genes lie within or proximal to Kcnq1. These data support the proposal that chromosomal abnormalities, including translocations, within KCNQ1 that are associated with the human disease Beckwith-Wiedemann syndrome (BWS) may disrupt CDKN1C expression. These results underscore the importance of gene clustering for the proper regulation of imprinted genes.
|Alternate Journal||Nat. Genet.|