The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins

Abstract.The HMG-box domain of ~75 amino acid residues was originally identified as the domain that mediates the DNA-binding of chromatin-associated high-mobility group (HMG) proteins of the HMGB type. In the last few years, HMG-box domains have been found in various DNA-binding proteins including transcription factors and subunits of chromatin-remodeling complexes. HMG-box domains mediate either non-sequence-specific (e.g., HMGB-type proteins) or sequence-specific (e.g., transcription factors) DNA binding. Both types of HMG-box domains bind non-B-type DNA structures (bent, kinked and unwound) with high affinity. In addition, HMG-box domains are involved in a variety of protein-protein interactions. Here, we have examined the human and plant genomes for genes encoding HMG-box domains. 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.

[1]  T. Tlsty Genomic instability and its role in neoplasia. , 1997, Current topics in microbiology and immunology.

[2]  Wai-In Chan,et al.  CIC, a member of a novel subfamily of the HMG-box superfamily, is transiently expressed in developing granule neurons. , 2002, Brain research. Molecular brain research.

[3]  G. Bauw,et al.  Protein Kinase CK2 Differentially Phosphorylates Maize Chromosomal High Mobility Group B (HMGB) Proteins Modulating Their Stability and DNA Interactions* , 2002, The Journal of Biological Chemistry.

[4]  L. Sessa,et al.  The evolution of High Mobility Group Box (HMGB) chromatin proteins in multicellular animals. , 2007, Gene.

[5]  J. Lichota,et al.  Differential chromatin association and nucleosome binding of the maize HMGA, HMGB, and SSRP1 proteins. , 2001, Biochemistry.

[6]  Wankee Kim,et al.  Association of human kinesin superfamily protein member 4 with BRCA2-associated factor 35. , 2003, The Biochemical journal.

[7]  A. Wolffe,et al.  Evidence for a shared structural role for HMG1 and linker histones B4 and H1 in organizing chromatin. , 1996, The EMBO journal.

[8]  T. Kidokoro,et al.  From SRY to SOX9: mammalian testis differentiation. , 2005, Journal of biochemistry.

[9]  E. Laue,et al.  Structure of the A-domain of HMG1 and its interaction with DNA as studied by heteronuclear three- and four-dimensional NMR spectroscopy. , 1995, Biochemistry.

[10]  A. Aguzzi,et al.  The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice , 1999, Nature Genetics.

[11]  J. Kaye,et al.  TOX defines a conserved subfamily of HMG-box proteins , 2003, BMC Genomics.

[12]  T. Merkle,et al.  The Arabidopsis genome encodes structurally and functionally diverse HMGB-type proteins. , 2006, Journal of molecular biology.

[13]  R. Broadhurst,et al.  DNA-binding properties of the tandem HMG boxes of high-mobility-group protein 1 (HMG1). , 1998, European journal of biochemistry.

[14]  P. Koopman,et al.  Sry and the hesitant beginnings of male development. , 2007, Developmental biology.

[15]  J. D. den Dunnen,et al.  WHSC1L1, on human chromosome 8p11.2, closely resembles WHSC1 and maps to a duplicated region shared with 4p16.3. , 2001, Genomics.

[16]  T. Merkle,et al.  HMGB6 from Arabidopsis thaliana specifies a novel type of plant chromosomal HMGB protein. , 2004, Biochemistry.

[17]  M. Bustin Revised nomenclature for high mobility group (HMG) chromosomal proteins. , 2001, Trends in biochemical sciences.

[18]  A. Grove,et al.  The Saccharomyces cerevisiae High Mobility Group Box Protein HMO1 Contains Two Functional DNA Binding Domains* , 2004, Journal of Biological Chemistry.

[19]  M. Bianchi,et al.  HMGB proteins and gene expression. , 2003, Current opinion in genetics & development.

[20]  Robin Lovell-Badge,et al.  A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif , 1990, Nature.

[21]  J. Brennan,et al.  One tissue, two fates: molecular genetic events that underlie testis versus ovary development , 2004, Nature Reviews Genetics.

[22]  J. Russell,et al.  RNA-polymerase-I-directed rDNA transcription, life and works. , 2005, Trends in biochemical sciences.

[23]  S. Landolfo,et al.  The high-mobility group protein T160 binds to both linear and cruciform DNA and mediates DNA bending as determined by ring closure. , 1997, Experimental cell research.

[24]  Jiří Fajkus,et al.  Telomeres in evolution and evolution of telomeres , 2005, Chromosome Research.

[25]  C. Verrijzer,et al.  Composition and functional specificity of SWI2/SNF2 class chromatin remodeling complexes. , 2005, Biochimica et biophysica acta.

[26]  M. Beltrame,et al.  Specific recognition of cruciform DNA by nuclear protein HMG1. , 1989, Science.

[27]  G. Längst,et al.  Nucleosome remodeling: one mechanism, many phenomena? , 2004, Biochimica et biophysica acta.

[28]  P. Cary,et al.  Solution structure of a DNA-binding domain from HMG1. , 1993, Nucleic acids research.

[29]  C. Janke,et al.  Drosophila DSP1 and rat HMGB1 have equivalent DNA binding properties and share a similar secondary fold. , 2003, Journal of biochemistry.

[30]  S. Brenner,et al.  Origin and diversity of the SOX transcription factor gene family: genome-wide analysis in Fugu rubripes. , 2004, Gene.

[31]  M. Cerone,et al.  Telomere maintenance by telomerase and by recombination can coexist in human cells. , 2001, Human molecular genetics.

[32]  D. Bodine,et al.  Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation. , 2003, Blood.

[33]  M. Wegner,et al.  From head to toes: the multiple facets of Sox proteins. , 1999, Nucleic acids research.

[34]  J. Alonso,et al.  Four differently chromatin-associated maize HMG domain proteins modulate DNA structure and act as architectural elements in nucleoprotein complexes. , 1998, The Plant journal : for cell and molecular biology.

[35]  J. Lichota,et al.  Ectopic expression of the maize chromosomal HMGB1 protein causes defects in root development of tobacco seedlings. , 2004, Biochemical and biophysical research communications.

[36]  R. C. Johnson,et al.  The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. , 1993, Genes & development.

[37]  C. Stemmer,et al.  Phosphorylation of maize and Arabidopsis HMGB proteins by protein kinase CK2alpha. , 2003, Biochemistry.

[38]  F. Yuan,et al.  Evidence for Involvement of HMGB1 Protein in Human DNA Mismatch Repair* , 2004, Journal of Biological Chemistry.

[39]  G M Clore,et al.  Structural basis for SRY-dependent 46-X,Y sex reversal: modulation of DNA bending by a naturally occurring point mutation. , 2001, Journal of molecular biology.

[40]  David A. Case,et al.  Structural basis for DNA bending by the architectural transcription factor LEF-1 , 1995, Nature.

[41]  D. Bodine,et al.  Hmgb3 deficiency deregulates proliferation and differentiation of common lymphoid and myeloid progenitors. , 2005, Blood.

[42]  G. Längst,et al.  The DNA chaperone HMGB1 facilitates ACF/CHRAC‐dependent nucleosome sliding , 2002, The EMBO journal.

[43]  R. Quatrano,et al.  Histone H1 Enhances the DNA Binding Activity of the Transcription Factor EmBP-1* , 1996, The Journal of Biological Chemistry.

[44]  R. Grosschedl,et al.  Regulation of LEF-1/TCF transcription factors by Wnt and other signals. , 1999, Current opinion in cell biology.

[45]  Jeon-Soo Shin,et al.  Nucleocytoplasmic Shuttling of HMGB 1 Is Regulated by Phosphorylation That Redirects It toward Secretion 1 , 2006 .

[46]  H. Schöler,et al.  Reduced fertility and spermatogenesis defects in mice lacking chromosomal protein Hmgb2. , 2001, Development.

[47]  C. Stemmer,et al.  Variability in Arabidopsis thaliana chromosomal high-mobility-group-1-like proteins. , 1997, European journal of biochemistry.

[48]  K. Grasser Plant chromosomal high mobility group (HMG) proteins. , 1995, The Plant journal : for cell and molecular biology.

[49]  D. Reinberg,et al.  Histone H2B Monoubiquitination Functions Cooperatively with FACT to Regulate Elongation by RNA Polymerase II , 2006, Cell.

[50]  D. Reinberg,et al.  de FACTo Nucleosome Dynamics* , 2006, Journal of Biological Chemistry.

[51]  J. Wiśniewski,et al.  HMG1 proteins from evolutionary distant organisms distort B-DNA conformation in similar way. , 1999, Biochimica et biophysica acta.

[52]  Qiang Wu,et al.  Rice HMGB1 protein recognizes DNA structures and bends DNA efficiently. , 2003, Archives of biochemistry and biophysics.

[53]  Hiroshi Shibuya,et al.  Negative regulation of Wnt signalling by HMG2L1, a novel NLK‐binding protein , 2003, Genes to cells : devoted to molecular & cellular mechanisms.

[54]  J. Bode,et al.  The binding sites for large and small high-mobility-group (HMG) proteins. Studies on HMG-nucleosome interactions in vitro. , 1982, European journal of biochemistry.

[55]  Peter Goodfellow,et al.  A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes , 1990, Nature.

[56]  P. Kraulis,et al.  Structure of the HMG box motif in the B‐domain of HMG1. , 1993, The EMBO journal.

[57]  V. Harley,et al.  The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]. , 2003, Endocrine reviews.

[58]  R. R. Samaha,et al.  Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes. , 2000, Science.

[59]  J. Grønlund,et al.  Overlapping expression patterns among the genes encoding Arabidopsis chromosomal high mobility group (HMG) proteins , 2007, FEBS letters.

[60]  Hua Lu,et al.  Human SSRP1 Has Spt16-dependent and -independent Roles in Gene Transcription* , 2007, Journal of Biological Chemistry.

[61]  M. Yaniv,et al.  Purification and biochemical heterogeneity of the mammalian SWI‐SNF complex. , 1996, The EMBO journal.

[62]  M. McDevitt,et al.  The HBP1 transcriptional repressor and the p38 MAP kinase: unlikely partners in G1 regulation and tumor suppression. , 2004, Gene.

[63]  G. Goodwin,et al.  A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. , 1973, European journal of biochemistry.

[64]  K. Ikuta,et al.  Borna Disease Virus Phosphoprotein Binds a Neurite Outgrowth Factor, Amphoterin/HMG-1 , 2001, Journal of Virology.

[65]  J. Friml,et al.  The chromatin remodelling complex FACT associates with actively transcribed regions of the Arabidopsis genome. , 2004, The Plant journal : for cell and molecular biology.

[66]  J. Svejstrup Chromatin elongation factors. , 2002, Current opinion in genetics & development.

[67]  J. Bernués,et al.  HMGB 1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences , 2001 .

[68]  A. Wurz,et al.  Isolation and characterization of high-mobility-group proteins from maize , 1991, Planta.

[69]  C. Stemmer,et al.  DNA-interactions and nuclear localisation of the chromosomal HMG domain protein SSRP1 from maize. , 2000, The Plant journal : for cell and molecular biology.

[70]  A. Nakagawara,et al.  HMGB1 and HMGB2 Cell-specifically Down-regulate the p53- and p73-dependent Sequence-specific Transactivation from the Human Bax Gene Promoter* , 2002, The Journal of Biological Chemistry.

[71]  K. Stott,et al.  Structure of a complex of tandem HMG boxes and DNA. , 2006, Journal of molecular biology.

[72]  J. Shay Telomerase in human development and cancer , 1997, Journal of cellular physiology.

[73]  M. Štros,et al.  Determinants of specific binding of HMGB1 protein to hemicatenated DNA loops. , 2005, Journal of molecular biology.

[74]  P. Koopman,et al.  Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators. , 2002, Current opinion in genetics & development.

[75]  A. Travers,et al.  HMG1 and 2, and related 'architectural' DNA-binding proteins. , 2001, Trends in biochemical sciences.

[76]  M. Bustin,et al.  HMG chromosomal proteins in development and disease. , 2007, Trends in cell biology.

[77]  R. Reddel,et al.  Suppression of Alternative Lengthening of Telomeres by Sp100-Mediated Sequestration of the MRE11/RAD50/NBS1 Complex , 2005, Molecular and Cellular Biology.

[78]  M. Weiss,et al.  Floppy SOX: mutual induced fit in hmg (high-mobility group) box-DNA recognition. , 2001, Molecular endocrinology.

[79]  R. Shiekhattar,et al.  A Human BRCA2 Complex Containing a Structural DNA Binding Component Influences Cell Cycle Progression , 2001, Cell.

[80]  T. Sternsdorf,et al.  Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif. , 1999, Journal of cell science.

[81]  K. Grasser,et al.  Interactions of the basic N-terminal and the acidic C-terminal domains of the maize chromosomal HMGB1 protein. , 2004, Biochemistry.

[82]  G. Goodwin,et al.  The BAH domain, polybromo and the RSC chromatin remodelling complex. , 2001, Gene.

[83]  Robert Tjian,et al.  Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins , 1990, Nature.

[84]  K. Vasquez,et al.  Interplay between human high mobility group protein 1 and replication protein A on psoralen-cross-linked DNA. , 2005, Biochemistry.

[85]  A. Belyavsky,et al.  Interaction of high mobility group proteins HMG 1 and HMG 2 with nucleosomes studied by gel electrophoresis , 1985, Molecular Biology Reports.

[86]  J. Štokrová,et al.  DNA looping by the HMG-box domains of HMG1 and modulation of DNA binding by the acidic C-terminal domain. , 1994, Nucleic acids research.

[87]  Kevin J. Tracey,et al.  High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal , 2005, Nature Reviews Immunology.

[88]  R. Lovell-Badge,et al.  Sox genes find their feet. , 1997, Current opinion in genetics & development.

[89]  S. Lippard,et al.  High-mobility-group 1 protein mediates DNA bending as determined by ring closures. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[90]  D. Housman,et al.  Isolation and characterization of human cDNA clones encoding a high mobility group box protein that recognizes structural distortions to DNA caused by binding of the anticancer agent cisplatin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[91]  P. Kraulis,et al.  Structure of the HMG box motif in the B‐domain of HMG1. , 1993, EMBO Journal.

[92]  James E Masse,et al.  The S. cerevisiae architectural HMGB protein NHP6A complexed with DNA: DNA and protein conformational changes upon binding. , 2002, Journal of molecular biology.

[93]  D. Bazett-Jones,et al.  Short-range DNA looping by the Xenopus HMG-box transcription factor, xUBF. , 1994, Science.

[94]  M. Bianchi,et al.  HMG proteins: dynamic players in gene regulation and differentiation. , 2005, Current opinion in genetics & development.

[95]  M. Beltrame,et al.  Hmg4, a new member of the Hmg1/2 gene family. , 1998, Genomics.

[96]  M. Gratacós,et al.  HMG20A and HMG20B map to human chromosomes 15q24 and 19p13.3 and constitute a distinct class of HMG-box genes with ubiquitous expression , 2000, Cytogenetic and Genome Research.

[97]  M. Štros,et al.  DNA bending by the chromosomal protein HMG1 and its high mobility group box domains. Effect of flanking sequences. , 1998, The Journal of biological chemistry.

[98]  Hans Clevers,et al.  T‐cell factors: turn‐ons and turn‐offs , 2002, The EMBO journal.

[99]  P. Sternberg,et al.  An HMG1-like protein facilitates Wnt signaling in Caenorhabditis elegans. , 1999, Genes & development.

[100]  M. Dai,et al.  SSRP1 functions as a co‐activator of the transcriptional activator p63 , 2002, The EMBO journal.

[101]  S. Yanagisawa,et al.  Specificity of the Stimulatory Interaction between Chromosomal HMGB Proteins and the Transcription Factor Dof2 and Its Negative Regulation by Protein Kinase CK2-mediated Phosphorylation* , 2002, The Journal of Biological Chemistry.

[102]  M. Hande,et al.  Yeast Nhp6A/B and Mammalian Hmgb1 Facilitate the Maintenance of Genome Stability , 2005, Current Biology.

[103]  Y. Nakamura,et al.  Cloning, characterization and chromosomal assignment of the human genes homologous to yeast PMS1, a member of mismatch repair genes. , 1994, Biochemical and biophysical research communications.

[104]  M. Štros,et al.  A Role of Basic Residues and the Putative Intercalating Phenylalanine of the HMG-1 Box B in DNA Supercoiling and Binding to Four-way DNA Junctions* , 2000, The Journal of Biological Chemistry.

[105]  N. Hamasaki,et al.  Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. , 2007, Mitochondrion.

[106]  A. Sinclair,et al.  Genetic evidence equating SRY and the testis-determining factor , 1990, Nature.

[107]  C. Stemmer,et al.  Protein kinase CK2 phosphorylates the HMG domain protein SSRP1 inducing the recognition of UV-damaged DNA , 2003 .

[108]  M. Bianchi,et al.  HMGB1: A signal of necrosis , 2007, Autoimmunity.

[109]  Jeon-Soo Shin,et al.  Nucleocytoplasmic Shuttling of HMGB1 Is Regulated by Phosphorylation That Redirects It toward Secretion1 , 2006, The Journal of Immunology.

[110]  A. Schulz,et al.  Arabidopsis Chromatin-Associated HMGA and HMGB Use Different Nuclear Targeting Signals and Display Highly Dynamic Localization within the Nucleus[W] , 2006, The Plant Cell Online.

[111]  A. Travers Priming the nucleosome: a role for HMGB proteins? , 2003, EMBO reports.

[112]  M. Thompson,et al.  Expression, purification and characterization of individual bromodomains from human Polybromo-1. , 2006, Protein expression and purification.

[113]  Michael Bustin,et al.  Regulation of DNA-Dependent Activities by the Functional Motifs of the High-Mobility-Group Chromosomal Proteins , 1999, Molecular and Cellular Biology.

[114]  S. Joos,et al.  Increased expression of high mobility group box 1 (HMGB1) is associated with an elevated level of the antiapoptotic c-IAP2 protein in human colon carcinomas , 2005, Gut.

[115]  E. Moran,et al.  DNA-binding properties of ARID family proteins , 2005, Nucleic acids research.

[116]  J. Y. Kim,et al.  Characterization of transgenic Arabidopsis plants overexpressing high mobility group B proteins under high salinity, drought or cold stress. , 2007, Plant & cell physiology.

[117]  H. Kondoh,et al.  Mechanism of Regulatory Target Selection by the SOX High-Mobility-Group Domain Proteins as Revealed by Comparison of SOX1/2/3 and SOX9 , 1999, Molecular and Cellular Biology.

[118]  J. Bernués,et al.  HMGB1 Interacts with Many Apparently Unrelated Proteins by Recognizing Short Amino Acid Sequences* , 2002, The Journal of Biological Chemistry.

[119]  C. Pabo,et al.  Basis for recognition of cisplatin-modified DNA by high-mobility-group proteins , 1999, Nature.

[120]  J. V. Sehy,et al.  Co-crystallization and preliminary crystallographic analysis of the high mobility group domain of HMG-D bound to DNA. , 1999, Acta crystallographica. Section D, Biological crystallography.

[121]  J. Alonso,et al.  Plant chromosomal HMGB proteins efficiently promote the bacterial site-specific beta-mediated recombination in vitro and in vivo. , 2002, Biochemistry.

[122]  Marion Grasser,et al.  Basic and acidic regions flanking the HMG-box domain of maize HMGB1 and HMGB5 modulate the stimulatory effect on the DNA binding of transcription factor Dof2. , 2007, Biochemistry.

[123]  Marion Grasser,et al.  High mobility group proteins of the plant HMGB family: dynamic chromatin modulators. , 2007, Biochimica et biophysica acta.

[124]  P. Dallas,et al.  ARID proteins: a diverse family of DNA binding proteins implicated in the control of cell growth, differentiation, and development. , 2002, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.