Alternative titles; symbols
HGNC Approved Gene Symbol: C1D
Cytogenetic location: 2p14 Genomic coordinates (GRCh38) : 2:68,041,130-68,063,004 (from NCBI)
Using RevErb (see 602408) as bait in a yeast 2-hybrid screen to identify nuclear hormone receptor corepressors, Zamir et al. (1997) cloned mouse C1d, which they called Sun-Cor, from a 17-day mouse embryo library. Sun-Cor encodes a highly basic 141-amino acid protein with a molecular mass of 16 kD. Northern blot analysis revealed expression of a 1.2-kb transcript in all 9 mouse tissues tested. Immunolocalization of Sun-Cor within transfected human kidney cells revealed a nuclear distribution.
Nehls et al. (1998) used anti-C1d antibody to clone C1d from a mouse cDNA expression library. By database searching with the mouse sequence, they identified a partial human clone. The full-length cDNA encodes a deduced 141-amino acid protein that shares 89% sequence identity with the mouse protein. Both proteins contain nuclear localization signals but no known DNA-binding motifs. Western blot analysis revealed expression of a 16-kD human protein, as well as a 32-kD band believed to be an SDS-resistant homodimer, in human fibroblasts. Immunolocalization studies revealed a nuclear fibrogranular distribution.
Using confocal microscopy in transfected HEp2 cells, Schilders et al. (2007) found that human C1D colocalized with MTR4 (MTREX; 618122) and the exosome component PMSCL100 (EXOSC10; 605960) in nucleoli.
Zamir et al. (1997) determined that Sun-Cor potentiates transcriptional repression by thyroid hormone receptor and RevErb in vivo, represses transcription when fused to a heterologous DNA-binding domain, and interacts with RevErb as well as with the thyroid hormone receptor in vitro. Sun-Cor also interacts with N-Cor (600849) and Smrt (600848) in vitro and with endogenous N-Cor in cultured cells. Zamir et al. (1997) also determined that Sun-Cor message and protein levels increase with differentiation of preadipocytes and myocytes in culture. Through mutation analysis, transfection, and expression of truncated message, they mapped the repression domain to the N-terminus. By cotransfection of RevErb and Sun-Cor followed by immunoprecipitation, direct interaction between these proteins was established. Similarly, they established direct interaction between Sun-Cor and N-Cor.
Nehls et al. (1998) confirmed DNA binding by recombinant mouse C1d protein in vitro through mobility shift assays and by electron microscopic visualization of C1d-DNA interaction. Electron microscopy suggested that C1d proteins preferentially bind existing C1d/DNA complexes.
Rothbarth et al. (2001) determined that cis-acting repressing sequences on the LINE-1 element of the promoter region could reduce transcriptional activity of the basal C1D promoter in human and murine cells by more than 95%.
Using knockdown experiments in transfected HEp2 cells, Schilders et al. (2007) demonstrated that nucleolar localization of C1D depended on its interaction with PMSCL100. Immunoprecipitation and pull-down assays showed that C1D and MPP6 (605500) bound simultaneously to PMSCL100 to form a trimeric complex in vitro. Knockdown assays demonstrated that MTR4, MPP6, and C1D were involved in maturation of 5.8S ribosomal RNA. Pull-down assays revealed that C1D was also able to bind RNA.
Rothbarth et al. (2001) identified an inverted LINE-1 repeat element in the C1D promoter and determined that the promoter may also contain a variant TATA box. It does not, however, contain a canonical TATA or CAAT box.
Haataja et al. (1998) mapped the C1D gene to chromosome 2. Rothbarth et al. (2001) refined the localization to chromosome 2p13-p12 based on sequence similarity between C1D and a BAC clone localized to this region. By sequence analysis, they also mapped a C1D pseudogene on chromosome 10.
Haataja, L., Groffen, J., Heisterkamp, N. Identification of a novel Rac3-interacting protein C1D. Int. J. Molec. Med. 1: 665-670, 1998. [PubMed: 9852280] [Full Text: https://doi.org/10.3892/ijmm.1.4.665]
Nehls, P., Keck, T., Greferath, R., Spiess, E., Glaser, T., Rothbarth, K., Stammer, H., Werner, D. cDNA cloning, recombinant expression and characterization of polypeptides with exceptional DNA affinity. Nucleic Acids Res. 26: 1160-1166, 1998. [PubMed: 9469821] [Full Text: https://doi.org/10.1093/nar/26.5.1160]
Rothbarth, K., Hunziker, A., Stammer, H., Werner, D. Promoter of the gene encoding the 16 kDa DNA-binding and apoptosis-inducing C1D protein. Biochim. Biophys. Acta 1518: 271-275, 2001. [PubMed: 11311939] [Full Text: https://doi.org/10.1016/s0167-4781(01)00198-1]
Schilders, G., van Dijk, E., Pruijn, G. J. M. C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing. Nucleic Acids Res. 35: 2564-2572, 2007. [PubMed: 17412707] [Full Text: https://doi.org/10.1093/nar/gkm082]
Zamir, I., Dawson, J., Lavinsky, R. M., Glass, C. K., Rosenfeld, M. G., Lazar, M. A. Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex. Proc. Nat. Acad. Sci. 94: 14400-14405, 1997. [PubMed: 9405624] [Full Text: https://doi.org/10.1073/pnas.94.26.14400]