Open AccessNonallelic Transcriptional Roles of CTCF and Cohesins at Imprinted Loci
Author(s) -
Shu Lin,
Anne C. Ferguson-Smith,
Richard M. Schultz,
Marisa S. Bartolomei
Publication year - 2011
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01449-10
Subject(s) - ctcf , cohesin , genomic imprinting , biology , imprinting (psychology) , genetics , locus (genetics) , x inactivation , gene , dna methylation , x chromosome , gene expression , chromosome , enhancer
The cohesin complex holds sister chromatids together and is essential for chromosome segregation. Recently, cohesins have been implicated in transcriptional regulation and insulation through genome-wide colocalization with the insulator protein CTCF, including involvement at the imprintedH19/Igf2 locus. CTCF binds to multiple imprinted loci and is required for proper imprinted expression at theH19/Igf2 locus. Here we report that cohesins colocalize with CTCF at two additional imprinted loci, theDlk1-Dio3 and theKcnq1/Kcnq1ot1 loci. Similar to theH19/Igf2 locus, CTCF and cohesins preferentially bind to theGtl2 differentially methylated region (DMR) on the unmethylated maternal allele. To determine the functional importance of the binding of CTCF and cohesins at the three imprinted loci, CTCF and cohesins were depleted in mouse embryonic fibroblast cells. The monoallelic expression of imprinted genes at these three loci was maintained. However, mRNA levels for these genes were typically increased; forH19 andIgf2 the increased level of expression was independent of the CTCF-binding sites in the imprinting control region. Results of these experiments demonstrate an unappreciated role for CTCF and cohesins in the repression of imprinted genes in somatic cells.