HGNC Approved Gene Symbol: CENPB
Cytogenetic location: 20p13 Genomic coordinates (GRCh38): 20:3,783,851-3,786,740 (from NCBI)
The structure and function of the centromere regions of mitotic chromosomes have been of interest to cell biologists, geneticists, and rheumatologists. Cell biologists focus on the centromere as both the site of sister chromatid pairing and the site of mitotic spindle attachment. The latter site, the kinetochore, is a trilaminar plaque structure embedded in the chromatin at the surface of the chromosome, as visualized by electron microscopy. Geneticists have been interested in centromeric sequences involved in the control of chromosomal segregation. Rheumatologists became interested in centromere structure when it was observed that centromere compounds are the target of autoimmune responses. Earnshaw et al. (1987) isolated a series of overlapping DNA clones for about 95% of the mRNA that encodes the B centromeric protein. Anticentromere antibodies recognize 3 antigens: CENPA (17 kD; 117139), CENPB (80 kD), and CENPC (140 kD; 117141). CENPB is considered the major centromere antigen, since antibody to it is consistently present at high titer in serum positive for anticentromere antibodies. The B protein is the product of a 2.9-kb mRNA that is encoded by a single locus.
CENPB recognition sequences, or CENPB boxes, appear at regular intervals in human centromeric alpha-satellite DNA (alphoid DNA). Using synthetic repeated DNA sequences, Ohzeki et al. (2002) found that the CENPB box and the alphoid DNA sequence were required for de novo mammalian artificial chromosome formation and assembly of functional centromere components, such as CENPA, CENPC, and CENPE (117143). Competitive chromatin immunoprecipitation assays showed that direct assembly of CENPA and CENPB in human cells with synthetic alphoid DNA required functional CENPB boxes.
Cam et al. (2008) described a genome surveillance mechanism for retrotransposons by transposase-derived centromeric protein CENPB homologs of the fission yeast Schizosaccharomyces pombe. CENPB homologs of S. pombe localize at and recruit histone deacetylases to silence Tf2 retrotransposons. CENPBs also repress solo long terminal repeats (LTRs) and LTR-associated genes. Tf2 elements are clustered into 'Tf' bodies, the organization of which depends on CENPBs that display discrete nuclear structures. Furthermore, CENPBs prevent an 'extinct' Tf1 retrotransposon from reentering the host genome by blocking its recombination with extant Tf2, and silence and immobilize a Tf1 integrant that becomes sequestered into Tf bodies. Cam et al. (2008) concluded that their results revealed a probably ancient retrotransposon surveillance pathway important for host genome integrity, and highlighted potential conflicts between DNA transposons and retrotransposons, major transposable elements believed to have greatly molded the evolution of genomes.
Okada et al. (2007) showed that human alphoid DNA arrays containing wildtype CENPB boxes were sufficient to direct assembly of CENPA-chromatin, de novo centromere formation, and stable artificial chromosome propagation in mouse embryonic fibroblasts expressing Cenpb. Centromere formation by Cenpb was suppressed when alpha-satellite DNA was integrated into a chromosomal site. At these sites, Cenpb enhanced both histone H3-K9 trimethylation and DNA methylation, thereby stimulating heterochromatin formation. Okada et al. (2007) proposed that CENPB plays dual antagonistic roles in modulating chromatin structure in centromeric satellite DNA, alternatively modulating assembly of CENPA chromatin and H3-K9 trimethylation.
By optimizing the primer-annealing temperature in a rapid air cycling procedure, Sugimoto et al. (1993) specifically amplified human DNA sequences encoding CENPB and CENPC, without any detectable amplification of highly homologous rodent DNA sequences. Using a panel of rodent/human hybrid DNAs, the human CENPB and CENPC genes were mapped to chromosomes 20 and 12, respectively. By fluorescence in situ hybridization, Seki et al. (1994) assigned the CENPB gene to 20p13.
Fowler et al. (2000) developed Cenpb null mice. These mice appeared normal but had reduced body weight and reduced testis or uterine weight. Reduction in body weight was dependent upon the genetic background and gender, but the reduction in gonad weight was independent of these variables. Cenpb null females of 2 different genetic backgrounds were reproductively competent but showed age-dependent reproductive deterioration leading to a complete breakdown at or before 9 months of age. Cenpb null females of a third genetic background were totally incompetent or were capable of producing no more than 1 litter. Histology of the uterus revealed normal myometrium and endometrium but grossly disrupted luminal and glandular epithelium. In situ hybridization of wildtype animals revealed high Cenpb expression in the uterine epithelium.
By indirect immunofluorescence and immunoblotting using serum from a patient with the CREST variant of scleroderma (181750), Kingwell and Rattner (1987) identified a 50-kD antigen located at the surface of the primary constrictions (kinetochore region) of both human and Indian muntjac chromosomes. The antigen had been designated centromeric protein D (CENPD).
Cam, H. P., Noma, K., Ebina, H., Levin, H. L., Grewal, S. I. S. Host genome surveillance for retrotransposons by transposon-derived proteins. Nature 451: 431-436, 2008. [PubMed: 18094683] [Full Text: https://doi.org/10.1038/nature06499]
Earnshaw, W. C., Sullivan, K. F., Machlin, P. S., Cooke, C. A., Kaiser, D. A., Pollard, T. D., Rothfield, N. F., Cleveland, D. W. Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen. J. Cell Biol. 104: 817-829, 1987. [PubMed: 2435739] [Full Text: https://doi.org/10.1083/jcb.104.4.817]
Fowler, K. J., Hudson, D. F., Salamonsen, L. A., Edmondson, S. R., Earle, E., Sibson, M. C., Choo, K. H. A. Uterine dysfunction and genetic modifiers in centromere protein B-deficient mice. Genome Res. 10: 30-41, 2000. [PubMed: 10645947]
Kingwell, B., Rattner, J. B. Mammalian kinetochore/centromere composition: a 50 kDa antigen is present in the mammalian kinetochore/centromere. Chromosoma 95: 403-407, 1987. [PubMed: 3315496] [Full Text: https://doi.org/10.1007/BF00333991]
Ohzeki, J., Nakano, M., Okada, T., Masumoto, H. CENP-B box is required for de novo centromere chromatin assembly on human alphoid DNA. J. Cell Biol. 159: 765-775, 2002. [PubMed: 12460987] [Full Text: https://doi.org/10.1083/jcb.200207112]
Okada, T., Ohzeki, J., Nakano, M., Yoda, K., Brinkley, W. R., Larionov, V., Masumoto, H. CENP-B controls centromere formation depending on the chromatin context. Cell 131: 1287-1300, 2007. [PubMed: 18160038] [Full Text: https://doi.org/10.1016/j.cell.2007.10.045]
Seki, N., Saito, T., Kitagawa, K., Masumoto, H., Okazaki, T., Hori, T.-A. Mapping of the human centromere protein B gene (CENPB) to chromosome 20p13 by fluorescence in situ hybridization. Genomics 24: 187-188, 1994. [PubMed: 7896278] [Full Text: https://doi.org/10.1006/geno.1994.1600]
Sugimoto, K., Yata, H., Himeno, M. Mapping of the human CENP-B gene to chromosome 20 and the CENP-C gene to chromosome 12 by a rapid cycle DNA amplification procedure. Genomics 17: 240-242, 1993. [PubMed: 8406460] [Full Text: https://doi.org/10.1006/geno.1993.1312]