hmgb proteins


Summary: A family of sequence-related proteins similar to HMGB1 PROTEIN that contains specific HMG-BOX DOMAINS.

Top Publications

  1. Yanai H, Ban T, Wang Z, Choi M, Kawamura T, Negishi H, et al. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature. 2009;462:99-103 pubmed publisher
    ..These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders. ..
  2. Catena R, Tiveron C, Ronchi A, Porta S, Ferri A, Tatangelo L, et al. Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. J Biol Chem. 2004;279:41846-57 pubmed
    ..Oct4 might play a role in the regulation of Sox2 in ES (inner cell mass) cells and, possibly, at the transition between inner cell mass and neural cells, before recruitment of neural POU factors such as Brn1 and Brn2. ..
  3. Bakrania P, Robinson D, Bunyan D, Salt A, Martin A, Crolla J, et al. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. Br J Ophthalmol. 2007;91:1471-6 pubmed
  4. Sisodiya S, Ragge N, Cavalleri G, Hever A, Lorenz B, Schneider A, et al. Role of SOX2 mutations in human hippocampal malformations and epilepsy. Epilepsia. 2006;47:534-42 pubmed
  5. Sakamoto Y, Hara K, Kanai Azuma M, Matsui T, Miura Y, Tsunekawa N, et al. Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos. Biochem Biophys Res Commun. 2007;360:539-44 pubmed
    ..This suggests the region-specific redundant activities of three SoxF members along the anteroposterior axis of embryonic vascular network. ..
  6. Tsukamoto T, Inada K, Tanaka H, Mizoshita T, Mihara M, Ushijima T, et al. Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia. J Cancer Res Clin Oncol. 2004;130:135-45 pubmed
    ..Immunohistochemical study confirmed decreased expression of Sox2 and ectopic emergence of Cdx2 protein in IM glands. Down-regulation of Sox2, besides ectopic expression of Cdx genes, may be important factors for the development of IM. ..
  7. Schrumpfová P, Fojtova M, Mokros P, Grasser K, Fajkus J. Role of HMGB proteins in chromatin dynamics and telomere maintenance in Arabidopsis thaliana. Curr Protein Pept Sci. 2011;12:105-11 pubmed
    ..b>HMGB proteins play important role in dynamic changes of chromatin structure and are involved in regulation of cellular ..
  8. Kondoh H, Uchikawa M, Kamachi Y. Interplay of Pax6 and SOX2 in lens development as a paradigm of genetic switch mechanisms for cell differentiation. Int J Dev Biol. 2004;48:819-27 pubmed
    ..Thus, the regulation of SOX2 (and SOX1/3) and its partner factors, exemplified by Pax6, determines the spatio-temporal order of the occurrence of cell differentiation. ..
  9. Gontan C, de Munck A, Vermeij M, Grosveld F, Tibboel D, Rottier R. Sox2 is important for two crucial processes in lung development: branching morphogenesis and epithelial cell differentiation. Dev Biol. 2008;317:296-309 pubmed publisher
    ..However, Sox2 overexpression does not lead to a complete abrogation of the epithelial differentiation program. ..

More Information


  1. Krohn N, Yanagisawa S, Grasser K. Specificity of the stimulatory interaction between chromosomal HMGB proteins and the transcription factor Dof2 and its negative regulation by protein kinase CK2-mediated phosphorylation. J Biol Chem. 2002;277:32438-44 pubmed
    ..Using the transcription factor Dof2 and five different maize HMGB proteins, we have examined the specificity of the HMGB-transcription factor interaction...
  2. Williamson K, Hever A, Rainger J, Rogers R, Magee A, Fiedler Z, et al. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Hum Mol Genet. 2006;15:1413-22 pubmed
    ..SOX2, with NMYC and CHD7, is now the third transcriptional regulator known to be critical for normal oesophageal development in humans...
  3. Becker N, Kahn J, Maher L. Eukaryotic HMGB proteins as replacements for HU in E. coli repression loop formation. Nucleic Acids Res. 2008;36:4009-21 pubmed publisher
    ..coli cells to explore the extent to which HMGB proteins and derivatives can complement a DNA looping defect in E. coli lacking HU protein...
  4. Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, et al. Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation. Proc Natl Acad Sci U S A. 2010;107:12611-6 pubmed publisher
    ..Chemopreventive approaches aimed at inhibiting the chronic inflammatory response, and especially blocking HMGB1, may decrease the risk of malignant mesothelioma among asbestos-exposed cohorts...
  5. Chew J, Loh Y, Zhang W, Chen X, Tam W, Yeap L, et al. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol. 2005;25:6031-46 pubmed
    ..Our data uncover a positive and potentially self-reinforcing regulatory loop that maintains Pou5f1 and Sox2 expression via the Oct4/Sox2 complex in pluripotent cells. ..
  6. Rodriguez Mari A, Yan Y, Bremiller R, Wilson C, Canestro C, Postlethwait J. Characterization and expression pattern of zebrafish Anti-Müllerian hormone (Amh) relative to sox9a, sox9b, and cyp19a1a, during gonad development. Gene Expr Patterns. 2005;5:655-67 pubmed
    ..The finding that zebrafish sox9b and sox8 were not co-expressed with amh in oocytes excludes the possibility that amh expression in zebrafish granulosa cells is directly regulated by either of these two genes. ..
  7. Bonneau D, Guichet A, Boussion F, Lépinard C, Biquard F, Descamps P. Absence of deletion at the SOX2 locus in a case of microphthalmia and esophageal atresia. Am J Med Genet A. 2004;131:204 pubmed
  8. Park K, Wells J, Zorn A, Wert S, Whitsett J. Sox17 influences the differentiation of respiratory epithelial cells. Dev Biol. 2006;294:192-202 pubmed
    ..Sites of expression and the effects of Sox17 in vivo and in vitro are consistent with a role for Sox17 or other members of the Sox family of transcription factors in differentiation of the conducting airway epithelium. ..
  9. Matsui T, Kanai Azuma M, Hara K, Matoba S, Hiramatsu R, Kawakami H, et al. Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice. J Cell Sci. 2006;119:3513-26 pubmed
    ..Therefore, our findings indicate that Sox17 and Sox18, and possibly all three SoxF genes, are cooperatively involved in mammalian vascular development. ..
  10. Kim I, Saunders T, Morrison S. Sox17 dependence distinguishes the transcriptional regulation of fetal from adult hematopoietic stem cells. Cell. 2007;130:470-83 pubmed
    ..Sox17 is thus required for the maintenance of fetal and neonatal HSCs and distinguishes their transcriptional regulation from adult HSCs. ..
  11. Niakan K, Ji H, Maehr R, Vokes S, Rodolfa K, Sherwood R, et al. Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal. Genes Dev. 2010;24:312-26 pubmed publisher
    ..By elaborating the function of Sox17, our results provide insight into how the transcriptional network promoting ES cell self-renewal is interrupted, allowing cellular differentiation. ..
  12. Frankenberg S, Gerbe F, Bessonnard S, Belville C, Pouchin P, Bardot O, et al. Primitive endoderm differentiates via a three-step mechanism involving Nanog and RTK signaling. Dev Cell. 2011;21:1005-13 pubmed publisher
    ..Thus, our results reveal three distinct phases in the PrE differentiation program. ..
  13. Avilion A, Nicolis S, Pevny L, Perez L, Vivian N, Lovell Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003;17:126-40 pubmed
    ..5 days postcoitum. Our data suggest that maternal components could be involved in establishing early cell fate decisions and that a combinatorial code, requiring SOX2 and OCT4, specifies the first three lineages present at implantation. ..
  14. Huang X, Gao X, Diaz Trelles R, Ruiz Lozano P, Wang Z. Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180. Dev Biol. 2008;319:258-66 pubmed publisher
    ..Together, these data reveal for the first time that BAF180 is critical for coronary vessel formation. ..
  15. Pedersen D, Grasser K. The role of chromosomal HMGB proteins in plants. Biochim Biophys Acta. 2010;1799:171-4 pubmed publisher
    ..In this article, we describe the family of HMGB proteins, which, in plants, are more diversified than in other eukaryotes...
  16. Verma A, Fitzpatrick D. Anophthalmia and microphthalmia. Orphanet J Rare Dis. 2007;2:47 pubmed
    ..The potential for visual development in microphthalmic patients is dependent upon retinal development and other ocular characteristics...
  17. Park I, Zhao R, West J, Yabuuchi A, Huo H, Ince T, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008;451:141-6 pubmed
    ..These data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture. ..
  18. Tani Y, Akiyama Y, Fukamachi H, Yanagihara K, Yuasa Y. Transcription factor SOX2 up-regulates stomach-specific pepsinogen A gene expression. J Cancer Res Clin Oncol. 2007;133:263-9 pubmed
    ..These data suggest that SOX2 plays an important role in regulation of pepsinogen A, and ectopic expression of SOX2 may be associated with abnormal differentiation of colorectal cancer cells. ..
  19. Launholt D, Merkle T, Houben A, Schulz A, Grasser K. Arabidopsis chromatin-associated HMGA and HMGB use different nuclear targeting signals and display highly dynamic localization within the nucleus. Plant Cell. 2006;18:2904-18 pubmed
    ..The HMGA proteins are characterized by the presence of four AT-hook DNA binding motifs, and the HMGB proteins contain an HMG box DNA binding domain...
  20. Chen Y, Shi L, Zhang L, Li R, Liang J, Yu W, et al. The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer. J Biol Chem. 2008;283:17969-78 pubmed publisher
    ..Our experiments not only determined a role for SOX2 in mammary tumorigenesis but also revealed another activity of the multifunctional protein, beta-catenin. ..
  21. Kim J, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature. 2008;454:646-50 pubmed publisher
    ..We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors. ..
  22. Stros M. HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta. 2010;1799:101-13 pubmed publisher
    b>HMGB proteins are members of the High Mobility Group (HMG) superfamily, possessing a unique DNA-binding domain, the HMG-box, which can bind non-B-type DNA structures (bent, kinked and unwound) with high affinity, and also distort DNA by ..
  23. Uchikawa M, Kamachi Y, Kondoh H. Two distinct subgroups of Group B Sox genes for transcriptional activators and repressors: their expression during embryonic organogenesis of the chicken. Mech Dev. 1999;84:103-20 pubmed
    ..g. interneurons of the spinal cord). These expression patterns suggest that target genes of Group B SOX proteins are finely regulated by the counterbalance of activating and repressing SOX proteins. ..
  24. Wilkinson B, Chen J, Han P, Rufner K, Goularte O, Kaye J. TOX: an HMG box protein implicated in the regulation of thymocyte selection. Nat Immunol. 2002;3:272-80 pubmed
    ..This molecular marker of thymic selection events may therefore play a role in establishing the activation threshold of developing T cells and patterning changes in gene expression. ..
  25. Chen Y, Jia X, Huang X, Zhang S, Li M, Xie J, et al. Two Litopenaeus vannamei HMGB proteins interact with transcription factors LvSTAT and LvDorsal to activate the promoter of white spot syndrome virus immediate-early gene ie1. Mol Immunol. 2011;48:793-9 pubmed publisher
    ..To our knowledge, this is the first report that invertebrate HMGB proteins participates in viral gene regulation.
  26. Ueno H, Matsuda T, Hashimoto S, Amaya F, Kitamura Y, Tanaka M, et al. Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med. 2004;170:1310-6 pubmed
    ..Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung. ..
  27. Launholt D, Grønlund J, Nielsen H, Grasser K. Overlapping expression patterns among the genes encoding Arabidopsis chromosomal high mobility group (HMG) proteins. FEBS Lett. 2007;581:1114-8 pubmed
    ..The differential HMG gene expression supports the view that the various HMG proteins serve partially different architectural functions in plant chromatin. ..
  28. Grasser K, Launholt D, Grasser M. High mobility group proteins of the plant HMGB family: dynamic chromatin modulators. Biochim Biophys Acta. 2007;1769:346-57 pubmed
    ..The HMGB proteins are abundant and highly mobile proteins in the cell nucleus that influence chromatin structure and enhance the ..
  29. Reeves R. Nuclear functions of the HMG proteins. Biochim Biophys Acta. 2010;1799:3-14 pubmed publisher
    ..The biological implications of having three architectural transcription factor families with complementary, but partially overlapping, nuclear functions are discussed. ..
  30. Schrode N, Saiz N, Di Talia S, Hadjantonakis A. GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst. Dev Cell. 2014;29:454-67 pubmed publisher
    ..This study provides a framework for quantitative analyses of mammalian embryos and establishes GATA6 as a nodal point in the gene regulatory network driving ICM lineage specification. ..
  31. Melvin V, Harrell C, Adelman J, Kraus W, Churchill M, Edwards D. The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB. J Biol Chem. 2004;279:14763-71 pubmed
    ..The CTE of both ER subtypes was also shown to be required for interaction with ERE half-sites. These studies reveal the importance of the CTE and HMGB-1/-2 for ERalpha and ERbeta interaction with their cognate target DNAs. ..
  32. Tatematsu M, Tsukamoto T, Inada K. Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia. Cancer Sci. 2003;94:135-41 pubmed
    ..Whether disturbance of the regulation of Sox2 and Cdx genes may be of importance to the biological behavior of gastric cancers should therefore be clarified in future studies. ..
  33. Uchikawa M, Ishida Y, Takemoto T, Kamachi Y, Kondoh H. Functional analysis of chicken Sox2 enhancers highlights an array of diverse regulatory elements that are conserved in mammals. Dev Cell. 2003;4:509-19 pubmed
    ..These functionally identified Sox2 enhancers exactly correspond to the extragenic sequence blocks conspicuously conserved between chicken and mammals, which are not discernible by sequence comparison among mammals. ..
  34. Graham T, Weaver C, Mao F, Kimelman D, Xu W. Crystal structure of a beta-catenin/Tcf complex. Cell. 2000;103:885-96 pubmed
    ..The structural and mutagenesis data reveal a potential target for molecular drug design studies. ..
  35. Sasai Y. Roles of Sox factors in neural determination: conserved signaling in evolution?. Int J Dev Biol. 2001;45:321-6 pubmed
    ..I also discuss the possible conservation of regulatory factors in neural differentiation, comparing Xenopus and Drosophila counterparts. ..
  36. Hock R, Furusawa T, Ueda T, Bustin M. HMG chromosomal proteins in development and disease. Trends Cell Biol. 2007;17:72-9 pubmed
    ..Here, we focus on the biological function of HMG proteins and highlight their possible roles in cellular differentiation and in the etiology of various diseases. ..
  37. Ferri A, Cavallaro M, Braida D, Di Cristofano A, Canta A, Vezzani A, et al. Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development. 2004;131:3805-19 pubmed
    ..These findings highlight a crucial and unexpected role for Sox2 in the maintenance of neurones in selected brain areas, and suggest a contribution of neural cell proliferative defects to the pathological phenotype. ..
  38. Clarke R, Yzaguirre A, Yashiro Ohtani Y, Bondue A, Blanpain C, Pear W, et al. The expression of Sox17 identifies and regulates haemogenic endothelium. Nat Cell Biol. 2013;15:502-10 pubmed publisher
    ..Taken together, these findings position Sox17 as a key regulator of haemogenic endothelial and haematopoietic development. ..
  39. Stemmer C, Fernandez S, Lopez G, Alonso J, Grasser K. Plant chromosomal HMGB proteins efficiently promote the bacterial site-specific beta-mediated recombination in vitro and in vivo. Biochemistry. 2002;41:7763-70 pubmed
    ..All analyzed HMGB proteins (HMGB1 to HMGB5) could promote beta recombination, but depending on the DNA substrate with different ..
  40. Parkinson D, Bhaskaran A, Arthur Farraj P, Noon L, Woodhoo A, Lloyd A, et al. c-Jun is a negative regulator of myelination. J Cell Biol. 2008;181:625-37 pubmed publisher
    ..Negative regulation of myelination is likely to have significant implications for three areas of Schwann cell biology: the molecular analysis of plasticity, demyelinating pathologies, and the response of peripheral nerves to injury...
  41. Zenteno J, Gascon Guzman G, Tovilla Canales J. Bilateral anophthalmia and brain malformations caused by a 20-bp deletion in the SOX2 gene. Clin Genet. 2005;68:564-6 pubmed
  42. Zhang W, Wu Q, Pwee K, Manjunatha Kini R. Interaction of wheat high-mobility-group proteins with four-way-junction DNA and characterization of the structure and expression of HMGA gene. Arch Biochem Biophys. 2003;409:357-66 pubmed
    ..Competition binding studies show that proteins share overlapping binding sites on four-way-junction DNA. HMGd does not bind to four-way-junction DNA. ..
  43. Stros M, Launholt D, Grasser K. The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins. Cell Mol Life Sci. 2007;64:2590-606 pubmed
    ..Compared to plants, human cells contain a larger variety of HMG-box proteins. Whereas in humans transcription factors are the most divergent group of HMG-box proteins, in plants the chromosomal HMGB-type proteins are most variable. ..
  44. Hagstrom S, Pauer G, Reid J, Simpson E, Crowe S, Maumenee I, et al. SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies. Am J Med Genet A. 2005;138A:95-8 pubmed
  45. Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, et al. Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol. 2006;26:7772-82 pubmed
    ..DNA microarray analysis revealed that a subset of putative Oct3/4 target genes may be regulated in the same manner. Our findings shed light on a novel function of Oct3/4 in ES cells. ..
  46. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861-72 pubmed
    ..Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts. ..
  47. Faivre L, Williamson K, Faber V, Laurent N, Grimaldi M, Thauvin Robinet C, et al. Recurrence of SOX2 anophthalmia syndrome with gonosomal mosaicism in a phenotypically normal mother. Am J Med Genet A. 2006;140:636-9 pubmed
  48. Grasser K. Chromatin-associated HMGA and HMGB proteins: versatile co-regulators of DNA-dependent processes. Plant Mol Biol. 2003;53:281-95 pubmed
    ..The HMGB proteins bind DNA non-sequence-specifically, but specifically recognise DNA structures...
  49. Bylund M, Andersson E, Novitch B, Muhr J. Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat Neurosci. 2003;6:1162-8 pubmed
    ..These data suggest that the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins. ..
  50. Kamachi Y, Uchikawa M, Kondoh H. Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet. 2000;16:182-7 pubmed
  51. Sinner D, Kordich J, Spence J, Opoka R, Rankin S, Lin S, et al. Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cells. Mol Cell Biol. 2007;27:7802-15 pubmed
    ..These findings indicate that Sox proteins can act as both antagonists and agonists of beta-catenin/TCF activity, and this mechanism may regulate Wnt signaling responses in many developmental and disease contexts. ..
  52. Remenyi A, Lins K, Nissen L, Reinbold R, Scholer H, Wilmanns M. Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev. 2003;17:2048-59 pubmed
    ..Interestingly, these surfaces frequently have redundant functions and are instrumental in recruiting various interacting protein partners. ..
  53. O Flaherty E, Kaye J. TOX defines a conserved subfamily of HMG-box proteins. BMC Genomics. 2003;4:13 pubmed
    ..In addition, our data suggest that the TOX subtype of HMG-box domain first appeared in invertebrates, was duplicated in early vertebrates and likely took on new functions in mammalian species. ..