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Complex regulation of a carbonic anhydrase gene cluster
Author(s) -
Lee JongJoo,
Song SangHyun,
Dean Ann
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.893.2
Subject(s) - enhancer , locus control region , ctcf , enhancer rnas , chromatin , locus (genetics) , biology , gene , binding site , promoter , microbiology and biotechnology , transcription factor , genetics , gene expression
The widely expressed nuclear factor LDB1, in a complex with erythroid DNA binding proteins GATA‐1 and SCL, occupies the beta‐globin locus control region and gene and is required for chromatin loop formation between these distant elements, which underlies LCR enhancer function. LDB1 is a widely expressed protein, suggesting it may facilitate long range enhancer interactions in multiple loci. We selected the carbonic anhydrase genes for further study of potential long range enhancer looping by LDB1 because CA1 and CA2 are strongly down‐regulated in MEL cells in which LDB1 had been reduced by shRNA. Using the ChIP assay, we validated LDB1 binding sites at the CA1 promoter and at two strong sites located ‐8 and ‐9 Kb upstream of CA2 in MEL cells that we considered to be a potential long range enhancer site. Unexpectedly, the enhancer blocking insulator protein CTCF occupied a site within the locus, potentially confounding enhancer function. Interestingly, 3C in erythroid cells showed long range interactions between the CTCF site, the potential LDB1 enhancer site and the promoters of the CA1 and CA2 genes. These results suggest an organizational role for CTCF in long range gene activation by an enhancer.