Alternative titles; symbols
HGNC Approved Gene Symbol: CIR1
Cytogenetic location: 2q31.1 Genomic coordinates (GRCh38) : 2:174,348,022-174,395,712 (from NCBI)
CBF1 (RBPJ; 147183) is a member of the CSL (CBF1, 'suppressor of hairless,' and Lag1) family of DNA-binding factors, which mediate transcriptional activation or repression. The Epstein-Barr virus-immortalizing protein EBNA2 activates both cellular and viral gene expression by targeting CBF1 and mimicking the NOTCH1 (190198) intracellular domain (NICD). Both NICD and EBNA2 bind to the repression domain of CBF1 and abolish repression activity. Using a yeast 2-hybrid screen of a B-cell cDNA library with CBF1 as bait, Hsieh et al. (1999) isolated a cDNA encoding CIR. The predicted 450-amino acid CIR protein contains a highly charged, serine-rich C terminus. Northern blot analysis revealed widespread expression of CIR, with strongest expression in heart, skeletal muscle, and pancreas. Immunofluorescence analysis showed that CIR is a nuclear protein like CBF1, although CIR did not bind to nucleolus.
Hsieh et al. (1999) found that the N-terminal 121 amino acids of CIR interacted with amino acids 233 to 249 of CBF1 and repressed transcriptional activity. Yeast 2-hybrid and immunofluorescence analyses showed that CIR also interacted with HDAC2 (605164) and SAP30 (603378), important mediators of transcriptional repression.
Gross (2012) mapped the CIR1 gene to chromosome 2q31.1 based on an alignment of the CIR1 sequence (GenBank AF098297) with the genomic sequence (GRCh37).
Gross, M. B. Personal Communication. Baltimore, Md. 9/11/2012.
Hsieh, J. J.-D., Zhou, S., Chen, L., Young, D. B., Hayward, S. D. CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex. Proc. Nat. Acad. Sci. 96: 23-28, 1999. [PubMed: 9874765] [Full Text: https://doi.org/10.1073/pnas.96.1.23]