Alternative titles; symbols
HGNC Approved Gene Symbol: HMGB2
Cytogenetic location: 4q34.1 Genomic coordinates (GRCh38): 4:173,331,376-173,334,358 (from NCBI)
The high mobility group (HMG) proteins are localized in the nuclei of higher eukaryotes and occur in 3 families, 1 of which includes HMG1 (163905) and HMG2. These proteins include a so-called HMG box which is involved in DNA binding. Both HMG1 and HMG2 proteins bind to single-stranded DNA, unwind double-stranded DNA, and increase transcription (summary by Wanschura et al., 1996).
By screening a human genomic library with the pig thymus cDNA coding for chromosomal protein HMG2, Shirakawa and Yoshida (1992) isolated a fragment containing the entire gene encoding this protein. Length of the mRNA predicted from the HMG2 exons was 1,125 bp. The primary structure of the human HMG2 protein consisted of 208 amino acid residues and was different from that of the pig Hgm2 in only 2 amino acids; one was exchanged and the other was missing.
In vivo transcription by RNA polymerase II (see 180660) takes place in the context of chromatin. Guermah et al. (2006) found that a purified, reconstituted RNA polymerase II system that sufficed for activator-dependent transcription on DNA templates was incapable of transcribing chromatin templates, even in the presence of factors that effected transcription in less-purified assay systems. Using a complementation and HeLa cell nuclear extract fractionation scheme, Guermah et al. (2006) identified and purified an activity, designated CTEA (chromatin transcription-enabling activity), that allowed for transcription through chromatin templates in a manner that was both activator and p300 (EP300; 602700)/acetyl-CoA dependent. CTEA acted primarily at the elongation step and enabled RNA polymerase II machinery to transcribe efficiently through several contiguously positioned nucleosomes. Guermah et al. (2006) identified the major functional component of CTEA as transcription elongation factor SII (TCEA1; 601425). SII was essential for productive transcription elongation, and its function at this step was dependent on p300-dependent acetylation. These synergistic transcriptional elongation activities were potentiated by HMGB2.
Using pull-down assays, Yanai et al. (2009) found that mouse HMGB proteins bound to all immunogenic nucleic acids, with a correlation between affinity and immunogenicity. Hmgb1 -/- and Hmgb2 -/- mouse cells were defective in type I interferon and inflammatory cytokine induction by DNA or RNA targeted to activate cytosolic nucleic acid-sensing receptors. Mouse cells in which expression of Hmgb1, Hmgb2, and Hmgb3 (300193) was suppressed by small interfering RNA also had impaired activation of transcription factors Irf3 (603734) and Nfkb (see 164011). The lack of HMGBs also resulted in poorer activation of Toll-like receptor-3 (Tlr3; 603029), Tlr7 (300365), and Tlr9 (605474) by their cognate nucleic acids (dsRNA, ssRNA, and hypomethylated DNA, respectively). Yanai et al. (2009) concluded that selective activation of nucleic acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs and may have implications for the treatment of immunologic disorders.
Shirakawa and Yoshida (1992) determined that the HMG2 is 2,665 bp long from the start site to the end of transcription and comprises 5 exons. The canonical 5-prime regulatory motifs, CCAAT, were present, whereas the TATA element was absent from the gene.
Wanschura et al. (1996) mapped the HMG2 gene to chromosome 4q31 by fluorescence in situ hybridization.
Guermah, M., Palhan, V. B., Tackett, A. J., Chait, B. T., Roeder, R. G. Synergistic functions of SII and p300 in productive activator-dependent transcription of chromatin templates. Cell 125: 275-286, 2006. [PubMed: 16630816] [Full Text: https://doi.org/10.1016/j.cell.2006.01.055]
Shirakawa, H., Yoshida, M. Structure of a gene coding for human HMG2 protein. J. Biol. Chem. 267: 6641-6645, 1992. [PubMed: 1551873]
Wanschura, S., Schoenmakers, E. F. P. M., Huysmans, C., Bartnitzke, S., Van de Ven, W. J. M., Bullerdiek, J. Mapping of the human HMG2 gene to 4q31. Genomics 31: 264-265, 1996. [PubMed: 8824816] [Full Text: https://doi.org/10.1006/geno.1996.0046]
Yanai, H., Ban, T., Wang, Z., Choi, M. K., Kawamura, T., Negishi, H., Nakasato, M., Lu, Y., Hangai, S., Koshiba, R., Savitsky, D., Ronfani, L., Akira, S., Bianchi, M. E., Honda, K., Tamura, T., Kodama, T., Taniguchi, T. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462: 99-103, 2009. [PubMed: 19890330] [Full Text: https://doi.org/10.1038/nature08512]