Alternative titles; symbols
HGNC Approved Gene Symbol: HMGN1
Cytogenetic location: 21q22.2 Genomic coordinates (GRCh38): 21:39,342,315-39,349,088 (from NCBI)
HMGN1 is a ubiquitous vertebrate nuclear protein that binds specifically to nucleosome core particles, the building blocks of the chromatin fiber. The dynamic interaction of HMGN1 with nucleosomes modulates the structure of chromatin and the levels of histone modifications, thereby playing a role in epigenetic regulation. Chromatin functions affected by HMGN1 include DNA repair and transcription (summary by Abuhatzira et al., 2011).
Landsman et al. (1989) obtained and sequenced genomic clones of HMG14. The deduced protein contains 99 amino acids.
Landsman et al. (1989) determined that the HMG14 gene contains 6 exons ranging in size from 30 to 839 bp. Two exons code for the entire DNA-binding site of the protein and have several features typical of housekeeping genes. Comparison with the human and chicken HMG17 gene (HMGN2; 163910), an analog of HMG14, showed that HMG14 and HMG17 both contain 6 exons and have exons of similar size, 5-prime regions highly enriched in GC residues, and features typical of housekeeping genes.
The human HMG14 multigene family is 1 of the largest retropseudogene families known. However, Landsman et al. (1989) found only a single genomic clone selected with a cDNA, thus suggesting that the human genome contains few and perhaps only 1 functional gene. Using human-rodent somatic cell hybrids, they localized the HMG14 gene to human chromosome 21. Petersen et al. (1990) used a GT dinucleotide repeat as a polymorphic marker in linkage analysis to demonstrate that the HMG14 locus is close to the ETS2 gene in band 21q22.3. By in situ hybridization, Pash et al. (1990) confirmed the assignment to 21q22.3.
Pash et al. (1990) analyzed expression of the Hmg14 gene in mouse embryos trisomic for chromosome 16 and found that trisomy 16 embryos had approximately 1.5 times more HMG14 mRNA and protein than their normal littermates. Pash et al. (1990) suggested that this nucleosomal binding protein may confer distinct properties to the chromatin structure of transcriptionally active genes and therefore may be a contributing factor in the development of Down syndrome (190685).
Since HMG14 is preferentially associated with transcriptionally active chromatin, Ding et al. (1994) assessed its effect on transcription by RNA polymerase II. They found that HMG14 enhanced transcription on chromatin templates but not on DNA templates. These findings suggested that the association of HMG14 with nucleosomes is part of the cellular process involved in the generation of transcriptionally active chromatin.
Sakai et al. (2003) presented evidence that ZNF219 (605036) represses transcription of HMGN1.
Using chromosome immunoprecipitation analysis and reporter gene assays with human T cells, Abuhatzira et al. (2011) found that HMGN1 bound regulatory regions overlapping the first exon of MECP2 (300005) and repressed MECP2 expression. In Down syndrome brain, quantitative PCR revealed increased HMGN1 and decreased MECP2 expression.
Abuhatzira et al. (2011) found that Hmgn1 -/- mice were hypoactive and displayed decreased exploratory behavior in an open field setting. In contrast, overexpression of human HMGN1 in transgenic mice led to hyperactivity and reduced anxiety. Both Hmgn1 -/- mice and HMGN1 transgenic mice showed abnormal, but distinct, social behaviors.
Abuhatzira, L., Shamir, A., Schones, D. E., Schaffer, A. A., Bustin, M. The chromatin-binding protein HMGN1 regulates the expression of methyl CpG-binding protein 2 (MECP2) and affects the behavior of mice. J. Biol. Chem. 286: 42051-42062, 2011. [PubMed: 22009741] [Full Text: https://doi.org/10.1074/jbc.M111.300541]
Ding, H.-F., Rimsky, S., Batson, S. C., Bustin, M., Hansen, U. Stimulation of RNA polymerase II elongation by chromosomal protein HMG-14. Science 265: 796-799, 1994. [PubMed: 8047885] [Full Text: https://doi.org/10.1126/science.8047885]
Landsman, D., McBride, O. W., Soares, N., Crippa, M. P., Srikantha, T., Bustin, M. Chromosomal protein HMG-14: identification, characterization, and chromosome localization of a functional gene from the large human multigene family. J. Biol. Chem. 264: 3421-3427, 1989. [PubMed: 2563381]
Pash, J., Popescu, N., Matocha, M., Rapoport, S., Bustin, M. Chromosomal protein HMG-14 gene maps to the Down syndrome region of human chromosome 21 and is overexpressed in mouse trisomy 16. Proc. Nat. Acad. Sci. 87: 3836-3840, 1990. [PubMed: 2140193] [Full Text: https://doi.org/10.1073/pnas.87.10.3836]
Petersen, M. B., Economou, E. P., Slaugenhaupt, S. A., Chakravarti, A., Antonarakis, S. E. Linkage analysis of the human HMG14 gene on chromosome 21 using a GT dinucleotide repeat as polymorphic marker. Genomics 7: 136-138, 1990. [PubMed: 1970797] [Full Text: https://doi.org/10.1016/0888-7543(90)90531-x]
Sakai, T., Hino, K., Wada, S., Maeda, H. Identification of the DNA binding specificity of the human ZNF219 protein and its function as a transcriptional repressor. DNA Res. 10: 155-165, 2003. [PubMed: 14621294] [Full Text: https://doi.org/10.1093/dnares/10.4.155]