non histone chromosomal architectural protein HMGI C


Gene Symbol: non histone chromosomal architectural protein HMGI C
Description: high mobility group AT-hook 2
Alias: Hmgic, high mobility group protein HMGI-C, non-histone chromosomal architectural protein HMGI-C
Species: rat

Top Publications

  1. Summer H, Li O, Bao Q, Zhan L, Peter S, Sathiyanathan P, et al. HMGA2 exhibits dRP/AP site cleavage activity and protects cancer cells from DNA-damage-induced cytotoxicity during chemotherapy. Nucleic Acids Res. 2009;37:4371-84 pubmed publisher
    ..Our study thus identifies an unexpected role for HMGA2 in DNA repair in cancer cells which has important clinical implications for disease diagnosis and therapy. ..
  2. Cattaruzzi G, Altamura S, Tessari M, Rustighi A, Giancotti V, Pucillo C, et al. The second AT-hook of the architectural transcription factor HMGA2 is determinant for nuclear localization and function. Nucleic Acids Res. 2007;35:1751-60 pubmed
    ..HMGA proteins are overexpressed and rearranged in a variety of tumors; our findings can thus help elucidating their role in neoplastic transformation. ..
  3. Li O, Vasudevan D, Davey C, Droge P. High-level expression of DNA architectural factor HMGA2 and its association with nucleosomes in human embryonic stem cells. Genesis. 2006;44:523-9 pubmed
  4. Narita M, Narita M, Krizhanovsky V, Nũnez S, Chicas A, Hearn S, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell. 2006;126:503-14 pubmed
    ..Our results identify a component of the senescence machinery that contributes to heterochromatin formation and imply that HMGA proteins also act in tumor suppressor networks. ..
  5. Chieffi P, Battista S, Barchi M, Di Agostino S, Pierantoni G, Fedele M, et al. HMGA1 and HMGA2 protein expression in mouse spermatogenesis. Oncogene. 2002;21:3644-50 pubmed
    ..Finally, few spermatids and complete absence of spermatozoa were observed in the testes of HMGA2-null mice, which suggests that the HMGA2 gene plays a critical role in male fertility. ..
  6. Cleynen I, Brants J, Peeters K, Deckers R, Debiec Rychter M, Sciot R, et al. HMGA2 regulates transcription of the Imp2 gene via an intronic regulatory element in cooperation with nuclear factor-kappaB. Mol Cancer Res. 2007;5:363-72 pubmed
    ..Finally, we provide evidence that there is a strong and statistically significant correlation between HMGA2 and IMP2 gene expression in human liposarcomas. ..
  7. Nishino J, Kim I, Chada K, Morrison S. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell. 2008;135:227-39 pubmed publisher
    ..Hmga2 thus promotes fetal and young-adult stem cell self-renewal by decreasing p16(Ink4a)/p19(Arf) expression. Changes in let-7 and Hmga2 expression during aging contribute to the decline in neural stem cell function. ..
  8. Zhou X, Benson K, Ashar H, Chada K. Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature. 1995;376:771-4 pubmed
    ..The HMGI proteins are known to be regulated by cell cycle-dependent phosphorylation which alters their DNA binding affinity. These results demonstrate the important role of HMGI proteins in mammalian growth and development. ..
  9. Li O, Li J, Droge P. DNA architectural factor and proto-oncogene HMGA2 regulates key developmental genes in pluripotent human embryonic stem cells. FEBS Lett. 2007;581:3533-7 pubmed
    ..Our results establish HMGA2 as a regulator of human genes linked to mesenchymal cell differentiation, adipogenesis, and hES cell growth. ..

More Information


  1. Boo L, Lin H, Chung V, Zhou B, Louie S, O Reilly M, et al. High mobility group A2 potentiates genotoxic stress in part through the modulation of basal and DNA damage-dependent phosphatidylinositol 3-kinase-related protein kinase activation. Cancer Res. 2005;65:6622-30 pubmed
    ..These findings should contribute to a greater understanding of the role of HMGA2 in promoting tumorigenesis and conveying (chemo)sensitivity towards doxorubicin and other related double-strand breaks. ..
  2. Borrmann L, Schwanbeck R, Heyduk T, Seebeck B, Rogalla P, Bullerdiek J, et al. High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity. Nucleic Acids Res. 2003;31:6841-51 pubmed
    ..Our results provide the first insights into how HMGA2 and its aberrant forms bind and regulate the ERCC1 promoter. ..
  3. Tessari M, Gostissa M, Altamura S, Sgarra R, Rustighi A, Salvagno C, et al. Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2. Mol Cell Biol. 2003;23:9104-16 pubmed
    ..These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation. ..
  4. Sinha Y, Wolff G, Baxter S, Domon O. Serum and pituitary concentrations of growth hormone and prolactin in pygmy mice. Proc Soc Exp Biol Med. 1979;162:221-3 pubmed
  5. Lin H, Xiong Y, Ho Y, Zhou B, Nguyen H, Deng H, et al. Transcriptional regulation by targeted expression of architectural transcription factor high mobility group A2 in salivary glands of transgenic mice. Eur J Oral Sci. 2007;115:30-9 pubmed
    ..Our findings indicate that the AQP-5 promoter/enhancer-containing region is sufficient to target salivary-specific transgene expression and suggest novel roles for HMGA2 in salivary epithelial cells. ..
  6. De Martino I, Visone R, Wierinckx A, Palmieri D, Ferraro A, Cappabianca P, et al. HMGA proteins up-regulate CCNB2 gene in mouse and human pituitary adenomas. Cancer Res. 2009;69:1844-50 pubmed publisher
    ..Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis. ..
  7. Cui T, Wei S, Brew K, Leng F. Energetics of binding the mammalian high mobility group protein HMGA2 to poly(dA-dT)2 and poly(dA)-poly(dT). J Mol Biol. 2005;352:629-45 pubmed
  8. Benson K, Chada K. Mini-mouse: phenotypic characterization of a transgenic insertional mutant allelic to pygmy. Genet Res. 1994;64:27-33 pubmed
    ..Therefore they should provide insight into the growth hormone-resistant human dwarfisms and help in furthering our knowledge of mammalian growth and development. ..
  9. Brants J, Ayoubi T, Chada K, Marchal K, Van de Ven W, Petit M. Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2. FEBS Lett. 2004;569:277-83 pubmed
    ..Our results clearly indicate that HMGA2 differentially regulates expression of IMP family members during embryogenesis. ..
  10. Chen B, Young J, Leng F. DNA bending by the mammalian high-mobility group protein AT hook 2. Biochemistry. 2010;49:1590-5 pubmed publisher
    ..The DNA bending angles were estimated to be 34.2 degrees , 33.5 degrees , and 35.4 degrees , respectively. ..
  11. Wang Y, Le Y, Xue J, Zheng Z, Xue Y. Let-7d miRNA prevents TGF-?1-induced EMT and renal fibrogenesis through regulation of HMGA2 expression. Biochem Biophys Res Commun. 2016;479:676-682 pubmed publisher
  12. Kitchen M, Yacqub Usman K, Emes R, Richardson A, Clayton R, Farrell W. Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells. Pituitary. 2015;18:674-84 pubmed publisher
    ..In addition to showing a mechanistic link between epigenetic modifications and miRNA expression these findings underscore their potential as therapeutic targets in this and other diseases. ..
  13. Ashar H, Fejzo M, Tkachenko A, Zhou X, Fletcher J, Weremowicz S, et al. Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Cell. 1995;82:57-65 pubmed
    ..These results, identifying a gene rearranged in a benign neoplastic process that does not proceed to a malignancy, suggest a role for HMGI-C in adipogenesis and mesenchyme differentiation. ..
  14. Zentner M, Lin H, Deng H, Kim K, Shih H, Ann D. Requirement for high mobility group protein HMGI-C interaction with STAT3 inhibitor PIAS3 in repression of alpha-subunit of epithelial Na+ channel (alpha-ENaC) transcription by Ras activation in salivary epithelial cells. J Biol Chem. 2001;276:29805-14 pubmed
    ..These findings delineate a network of inhibitory signaling pathways that converge on HMGI-C.PIAS3 complex, causally associating Ras/ERK activation with the repression of both GR and STAT3 signaling pathways in salivary epithelial cells. ..
  15. Li A, Boo L, Wang S, Lin H, Wang C, Yen Y, et al. Suppression of nonhomologous end joining repair by overexpression of HMGA2. Cancer Res. 2009;69:5699-706 pubmed publisher
    ..In summary, a novel role for HMGA2 to interfere with NHEJ processes was uncovered, implicating HMGA2 in the promotion of genome instability and tumorigenesis. ..
  16. Sanosaka T, Namihira M, Asano H, Kohyama J, Aisaki K, Igarashi K, et al. Identification of genes that restrict astrocyte differentiation of midgestational neural precursor cells. Neuroscience. 2008;155:780-8 pubmed publisher
    ..Taken together, our data suggest that astrocyte differentiation of NPCs is regulated not only by DNA methylation but also by genes whose expression is controlled spatio-temporally during brain development. ..
  17. Li D, Lin H, McMahon M, Ma H, Ann D. Oncogenic raf-1 induces the expression of non-histone chromosomal architectural protein HMGI-C via a p44/p42 mitogen-activated protein kinase-dependent pathway in salivary epithelial cells. J Biol Chem. 1997;272:25062-70 pubmed
    ..Altogether, these findings support the notion that the Raf/MEK/ERK signaling module, at least in part, regulates transcriptional activation of the chromosomal architectural protein HMGI-C. ..
  18. Crombez K, Vanoirbeek E, Van de Ven W, Petit M. Transactivation functions of the tumor-specific HMGA2/LPP fusion protein are augmented by wild-type HMGA2. Mol Cancer Res. 2005;3:63-70 pubmed
    ..These results support the concept that the transactivation functions of the novel HMGA2/LPP transcription factor contribute to lipomagenesis. ..
  19. Anand A, Chada K. In vivo modulation of Hmgic reduces obesity. Nat Genet. 2000;24:377-80 pubmed
    The HMGI family of proteins consists of three members, HMGIC, HMGI and HMGI(Y), that function as architectural factors and are essential components of the enhancesome...
  20. Zhu S, Deng S, Ma Q, Zhang T, Jia C, Zhuo D, et al. MicroRNA-10A* and MicroRNA-21 modulate endothelial progenitor cell senescence via suppressing high-mobility group A2. Circ Res. 2013;112:152-64 pubmed publisher
    ..miR-10A* and miR-21 regulate EPC senescence via suppressing Hmga2 expression and modulation of microRNAs may represent a potential therapeutic intervention in improving EPC-mediated angiogenesis and vascular repair. ..
  21. Rimoin D, Richmond L. The pygmy (pg) mutant of the mouse--a model of the human pygmy. J Clin Endocrinol Metab. 1972;35:467-8 pubmed
  22. Winter N, Nimzyk R, Bösche C, Meyer A, Bullerdiek J. Chromatin immunoprecipitation to analyze DNA binding sites of HMGA2. PLoS ONE. 2011;6:e18837 pubmed publisher
    ..The flanking regions are AT-rich, whereas a lower conservation is present in the center of the sequences. ..
  23. Di Agostino S, Fedele M, Chieffi P, Fusco A, Rossi P, Geremia R, et al. Phosphorylation of high-mobility group protein A2 by Nek2 kinase during the first meiotic division in mouse spermatocytes. Mol Biol Cell. 2004;15:1224-32 pubmed
    ..Because hmga2-/- mice are sterile and show a dramatic impairment of spermatogenesis, it is possible that the functional interaction between HMGA2 and Nek2 plays a crucial role in the correct process of chromatin condensation in meiosis. ..
  24. Winkler S, Murua Escobar H, Meyer B, Simon D, Eberle N, Baumgartner W, et al. HMGA2 expression in a canine model of prostate cancer. Cancer Genet Cytogenet. 2007;177:98-102 pubmed
    ..Thus, canine prostate cancer represents a spontaneously occurring model to test therapeutic effects resulting from reduced expression of HMGA2. ..
  25. Diana F, Di Bernardo J, Sgarra R, Tessari M, Rustighi A, Fusco A, et al. Differential HMGA expression and post-translational modifications in prostatic tumor cells. Int J Oncol. 2005;26:515-20 pubmed
    ..These data suggest exploring HMGA2 as a potential marker in human prostate tumor and moreover indicate PTMs as an additional tool in the staging of tumor progression. ..
  26. KING J. Pygmy, a dwarfing gene in the house mouse. J Hered. 1950;41:249-52 pubmed
  27. Xia X, Ahmad I. let-7 microRNA regulates neurogliogenesis in the mammalian retina through Hmga2. Dev Biol. 2016;410:70-85 pubmed publisher
    ..Thus, our observations suggest that let-7 promotes differentiation, regardless of the neuronal or glial lineage, shifting the balance from RPCs' maintenance to their differentiation in the developing retina. ..
  28. Malek A, Bakhidze E, Noske A, Sers C, Aigner A, Schafer R, et al. HMGA2 gene is a promising target for ovarian cancer silencing therapy. Int J Cancer. 2008;123:348-356 pubmed publisher
    ..The tumor growth inhibition effect of HMGA2 silencing for Ovcar-3 cells was validated in vivo. Our findings revealed that the HMGA2 gene represents a promising target for gene silencing therapy in ovarian cancer. ..
  29. Richter A, Lübbing M, Frank H, Nolte I, Bullerdiek J, von Ahsen I. High-mobility group protein HMGA2-derived fragments stimulate the proliferation of chondrocytes and adipose tissue-derived stem cells. Eur Cell Mater. 2011;21:355-63 pubmed
    ..Due to its proliferation inducing function and vast availability, this peptide is thus suitable for further application and investigation in various fields such as tissue engineering and stem cell research. ..
  30. Vallone D, Battista S, Pierantoni G, Fedele M, Casalino L, Santoro M, et al. Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product. EMBO J. 1997;16:5310-21 pubmed
  31. Thuault S, Tan E, Peinado H, Cano A, Heldin C, Moustakas A. HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem. 2008;283:33437-46 pubmed publisher
    ..The data propose that HMGA2 acts in a gene-specific manner to orchestrate the transcriptional network necessary for the EMT program. ..
  32. Bai Y, Wang J, Yang M, Zeng Y, Jiang H. SiRNA-HMGA2 weakened AGEs-induced epithelial-to-mesenchymal transition in tubular epithelial cells. Biochem Biophys Res Commun. 2015;457:730-5 pubmed publisher
    ..Collectively, these studies suggest that HMGA2 plays a important role in EMT during Diabetic nephropathy and more study toward HMGA2 should be played in renal pathogenesis. ..
  33. Shlapobersky M, Sanders R, Clark C, Spector D. Repression of HMGA2 gene expression by human cytomegalovirus involves the IE2 86-kilodalton protein and is necessary for efficient viral replication and inhibition of cyclin A transcription. J Virol. 2006;80:9951-61 pubmed
  34. Kazmierczak B, Pohnke Y, Bullerdiek J. Fusion transcripts between the HMGIC gene and RTVL-H-related sequences in mesenchymal tumors without cytogenetic aberrations. Genomics. 1996;38:223-6 pubmed
    ..Because of these cytogenetic aberrations the HMGI-C gene (HGMW-approved symbol HMGIC) becomes rearranged, with most of the breakpoints located in the large intron 3...