151. Nonallelic Transcriptional Roles of CTCF and Cohesins at Imprinted Loci
- Author
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Anne C. Ferguson-Smith, Shu Lin, Marisa S. Bartolomei, and Richard M. Schultz
- Subjects
CCCTC-Binding Factor ,Chromatin Immunoprecipitation ,RNA, Untranslated ,Transcription, Genetic ,Cohesin complex ,Chromosomal Proteins, Non-Histone ,Gene Expression ,Cell Cycle Proteins ,Locus (genetics) ,Chromatids ,Biology ,Insulator (genetics) ,Polymerase Chain Reaction ,Cell Line ,Genomic Imprinting ,Mice ,Insulin-Like Growth Factor II ,Chromosome Segregation ,Genes, Regulator ,Animals ,Gene Silencing ,RNA, Messenger ,RNA, Small Interfering ,Molecular Biology ,Genetics ,Cohesin ,KCNQ1OT1 ,Calcium-Binding Proteins ,Proteins ,Articles ,Cell Biology ,DNA Methylation ,Fibroblasts ,female genital diseases and pregnancy complications ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Repressor Proteins ,Gene Expression Regulation ,CTCF ,KCNQ1 Potassium Channel ,DNA methylation ,Intercellular Signaling Peptides and Proteins ,RNA, Long Noncoding ,biological phenomena, cell phenomena, and immunity ,Genomic imprinting - Abstract
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 imprinted H19/Igf2 locus. CTCF binds to multiple imprinted loci and is required for proper imprinted expression at the H19/Igf2 locus. Here we report that cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci. Similar to the H19/Igf2 locus, CTCF and cohesins preferentially bind to the Gtl2 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; for H19 and Igf2 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.
- Published
- 2011
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