The characterization of macroH2A beyond vertebrates supports an ancestral origin and conserved role for histone variants in chromatin

References

• Bonisch C, Hake SB. Histone H2A variants in nucleosomes and chromatin: more or less stable? Nucleic Acids Res 2012; 40:10719-41; PMID:23002134; http://dx.doi.org/10.1093/nar/gks865
   PubMed Web of Science ®Google Scholar
• Ausió J, Abbott DW. The many tales of a tail: carboxyl-terminal tail heterogeneity specializes histone H2A variants for defined chromatin function. Biochemistry 2002; 41:5945-9; PMID:11993987; http://dx.doi.org/10.1021/bi020059d
   PubMed Web of Science ®Google Scholar
• Pehrson JR, Fried VA. MacroH2A, a core histone containing a large nonhistone region. Science 1992; 257:1398-400; PMID:1529340; http://dx.doi.org/10.1126/science.1529340
   PubMed Web of Science ®Google Scholar
• Costanzi C, Pehrson JR. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 1998; 393:599-601; PMID:9634239; http://dx.doi.org/10.1038/31275
   PubMed Web of Science ®Google Scholar
• Costanzi C, Pehrson JR. MACROH2A2, a new member of the MARCOH2A core histone family. J Biol Chem 2001; 276:21776-84; PMID:11262398; http://dx.doi.org/10.1074/jbc.M010919200
   PubMed Web of Science ®Google Scholar
• Richler C, Dhara SK, Wahrman J. Histone macroH2A1.2 is concentrated in the XY compartment of mammalian male meiotic nuclei. Cytogenet Cell Genet 2000; 89:118-20; PMID:10894952; http://dx.doi.org/10.1159/000015589
   PubMedGoogle Scholar
• Rasmussen TP, Mastrangelo MA, Eden A, Pehrson JR, Jaenisch R. Dynamic relocalization of histone MacroH2A1 from centrosomes to inactive X chromosomes during X inactivation. J Cell Biol 2000; 150:1189-98; PMID:10974005; http://dx.doi.org/10.1083/jcb.150.5.1189
   PubMed Web of Science ®Google Scholar
• Mermoud JE, Costanzi C, Pehrson JR, Brockdorff N. Histone macroH2A1.2 relocates to the inactive X chromosome after initiation and propagation of X-inactivation. J Cell Biol 1999; 147:1399-408; PMID:10613899; http://dx.doi.org/10.1083/jcb.147.7.1399
   PubMed Web of Science ®Google Scholar
• Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, et al. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 2005; 8:19-30; PMID:15621527; http://dx.doi.org/10.1016/j.devcel.2004.10.019
   PubMed Web of Science ®Google Scholar
• Gamble MJ, Frizzell KM, Yang C, Krishnakumar R, Kraus WL. The histone variant macroH2A1 marks repressed autosomal chromatin, but protects a subset of its target genes from silencing. Genes Dev 2010; 24:21-32; PMID:20008927; http://dx.doi.org/10.1101/gad.1876110
   PubMed Web of Science ®Google Scholar
• Changolkar LN, Singh G, Cui K, Berletch JB, Zhao K, Disteche CM, Pehrson JR. Genome-wide distribution of macroH2A1 histone variants in mouse liver chromatin. Mol Cell Biol 2010; 30:5473-83; PMID:20937776; http://dx.doi.org/10.1128/MCB.00518-10
   PubMed Web of Science ®Google Scholar
• Ouararhni K, Hadj-Slimane R, Ait-Si-Ali S, Robin P, Mietton F, Harel-Bellan A, Dimitrov S, Hamiche A. The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity. Genes Dev 2006; 20:3324-36; PMID:17158748; http://dx.doi.org/10.1101/gad.396106
   PubMed Web of Science ®Google Scholar
• Creppe C, Posavec M, Douet J, Buschbeck M. MacroH2A in stem cells: a story beyond gene repression. Epigenomics 2012; 4:221-7; PMID:22449192; http://dx.doi.org/10.2217/epi.12.8
   PubMed Web of Science ®Google Scholar
• Rasmussen TP, Huang T, Mastrangelo MA, Loring J, Panning B, Jaenisch R. Messenger RNAs encoding mouse histone macroH2A1 isoforms are expressed at similar levels in male and female cells and result from alternative splicing. Nucleic Acids Res 1999; 27:3685-9; PMID:10471737; http://dx.doi.org/10.1093/nar/27.18.3685
   PubMed Web of Science ®Google Scholar
• Pehrson JR, Costanzi C, Dharia C. Developmental and tissue expression patterns of histone macroH2A1 subtypes. J Cell Biochem 1997; 65:107-13; PMID:9138085; http://dx.doi.org/10.1002/(SICI)1097-4644(199704)65:1%3c107::AID-JCB11%3e3.0.CO;2-H
   PubMed Web of Science ®Google Scholar
• Araya I, Nardocci G, Morales J, Vera M, Molina A, Alvarez M. MacroH2A subtypes contribute antagonistically to the transcriptional regulation of the ribosomal cistron during seasonal acclimatization of the carp fish. Epigenetics Chromatin 2010; 3:14; PMID:20670405; http://dx.doi.org/10.1186/1756-8935-3-14
   PubMed Web of Science ®Google Scholar
• Pehrson JR, Changolkar LN, Costanzi C, Leu NA. Mice without macroH2A histone variants. Mol Cell Biol 2014; 34:4523-33; PMID:25312643; http://dx.doi.org/10.1128/MCB.00794-14
   PubMed Web of Science ®Google Scholar
• Chang CC, Gao S, Sung LY, Corry GN, Ma Y, Nagy ZP, Tian XC, Rasmussen TP. Rapid elimination of the histone variant MacroH2A from somatic cell heterochromatin after nuclear transfer. Cell Reprogram 2010; 12:43-53; PMID:20132012; http://dx.doi.org/10.1089/cell.2009.0043
   PubMed Web of Science ®Google Scholar
• Creppe C, Janich P, Cantarino N, Noguera M, Valero V, Musulen E, Douet J, Posavec M, Martin-Caballero J, Sumoy L, et al. MacroH2A1 regulates the balance between self-renewal and differentiation commitment in embryonic and adult stem cells. Mol Cell Biol 2012; 32:1442-52; PMID:22331466; http://dx.doi.org/10.1128/MCB.06323-11
   PubMed Web of Science ®Google Scholar
• Gaspar-Maia A, Qadeer ZA, Hasson D, Ratnakumar K, Leu NA, Leroy G, Liu S, Costanzi C, Valle-Garcia D, Schaniel C, et al. MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency. Nat Commun 2013; 4:1565; PMID:23463008; http://dx.doi.org/10.1038/ncomms2582
   PubMed Web of Science ®Google Scholar
• Buschbeck M, Uribesalgo I, Wibowo I, Rue P, Martin D, Gutierrez A, Morey L, Guigo R, Lopez-Schier H, Di Croce L. The histone variant macroH2A is an epigenetic regulator of key developmental genes. Nat Struct Mol Biol 2009; 16:1074-9; PMID:19734898; http://dx.doi.org/10.1038/nsmb.1665
   PubMed Web of Science ®Google Scholar
• Changolkar LN, Costanzi C, Leu NA, Chen D, McLaughlin KJ, Pehrson JR. Developmental changes in histone macroH2A1-mediated gene regulation. Mol Cell Biol 2007; 27:2758-64; PMID:17242180; http://dx.doi.org/10.1128/MCB.02334-06
   PubMed Web of Science ®Google Scholar
• Monteiro FL, Baptista T, Amado F, Vitorino R, Jeronimo C, Helguero LA. Expression and functionality of histone H2A variants in cancer. Oncotarget 2014; 5:3428-43; PMID:25003966; http://dx.doi.org/10.18632/oncotarget.2007
   PubMed Web of Science ®Google Scholar
• Dardenne E, Pierredon S, Driouch K, Gratadou L, Lacroix-Triki M, Espinoza MP, Zonta E, Germann S, Mortada H, Villemin JP, et al. Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness. Nat Struct Mol Biol 2012; 19:1139-46; PMID:23022728; http://dx.doi.org/10.1038/nsmb.2390
   PubMed Web of Science ®Google Scholar
• Novikov L, Park JW, Chen H, Klerman H, Jalloh AS, Gamble MJ. QKI-mediated alternative splicing of the histone variant MacroH2A1 regulates cancer cell proliferation. Mol Cell Biol 2011; 31:4244-55; PMID:21844227; http://dx.doi.org/10.1128/MCB.05244-11
   PubMed Web of Science ®Google Scholar
• Abbott DW, Laszczak M, Lewis JD, Su H, Moore SC, Hills M, Dimitrov S, Ausio J. Structural characterization of macroH2A containing chromatin. Biochemistry 2004; 43:1352-9; PMID:14756572; http://dx.doi.org/10.1021/bi035859i
   PubMed Web of Science ®Google Scholar
• Chakravarthy S, Luger K. The histone variant macro-H2A preferentially forms “hybrid nucleosomes”. J Biol Chem 2006; 281:25522-31; PMID:16803903; http://dx.doi.org/10.1074/jbc.M602258200
   PubMed Web of Science ®Google Scholar
• Angelov D, Molla A, Perche PY, Hans F, Cote J, Khochbin S, Bouvet P, Dimitrov S. The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling. Mol Cell 2003; 11:1033-41; PMID:12718888; http://dx.doi.org/10.1016/S1097-2765(03)00100-X
   PubMed Web of Science ®Google Scholar
• Muthurajan UM, McBryant SJ, Lu X, Hansen JC, Luger K. The linker region of macroH2A promotes self-association of nucleosomal arrays. J Biol Chem 2011; 286:23852-64; PMID:21532035; http://dx.doi.org/10.1074/jbc.M111.244871
   PubMed Web of Science ®Google Scholar
• Chakravarthy S, Patel A, Bowman GD. The basic linker of macroH2A stabilizes DNA at the entry/exit site of the nucleosome. Nucleic Acids Res 2012; 40:8285-95; PMID:22753032; http://dx.doi.org/10.1093/nar/gks645
   PubMed Web of Science ®Google Scholar
• Chakravarthy S, Gundimella SK, Caron C, Perche PY, Pehrson JR, Khochbin S, Luger K. Structural characterization of the histone variant macroH2A. Mol Cell Biol 2005; 25:7616-24; PMID:16107708; http://dx.doi.org/10.1128/MCB.25.17.7616-7624.2005
   PubMed Web of Science ®Google Scholar
• Nusinow DA, Hernandez-Munoz I, Fazzio TG, Shah GM, Kraus WL, Panning B. Poly(ADP-ribose) polymerase 1 is inhibited by a histone H2A variant, MacroH2A, and contributes to silencing of the inactive X chromosome. J Biol Chem 2007; 282:12851-9; PMID:17322296; http://dx.doi.org/10.1074/jbc.M610502200
   PubMed Web of Science ®Google Scholar
• Henikoff S, Smith MM. Histone variants and epigenetics. Cold Spring Harb Perspect Biol 2015; 7:a019364; PMID:25561719; http://dx.doi.org/10.1101/cshperspect.a019364
   PubMed Web of Science ®Google Scholar
• Talbert PB, Ahmad K, Almouzni G, Ausio J, Berger F, Bhalla PL, Bonner WM, Cande WZ, Chadwick BP, Chan SW, et al. A unified phylogeny-based nomenclature for histone variants. Epigenetics Chromatin 2012; 5:7; PMID:22650316; http://dx.doi.org/10.1186/1756-8935-5-7
   PubMed Web of Science ®Google Scholar
• Eirín-López JM, González-Romero R, Dryhurst D, Méndez J, Ausió J. Long-term evolution of histone families: old notions and new insights into their diversification mechanisms across eukaryotes. In: Pontarotti P, ed. Evolutionary Biology: Concept, Modeling, and Application. Berlin Heidelberg: Springer-Verlag, 2009:139-62; http://dx.doi.org/10.1007/978-3-642-00952-5_8
   Google Scholar
• Gonzalez-Romero R, Ausio J, Mendez J, Eirin-Lopez JM. Early evolution of histone genes: prevalence of an 'orphon' H1 lineage in protostomes and birth-and-death process in the H2A family. J Mol Evol 2008; 66:505-18; PMID:18443735; http://dx.doi.org/10.1007/s00239-008-9109-1
   PubMed Web of Science ®Google Scholar
• Kasinsky H, Lewis J, Dacks J, Ausió J. Origin of H1 linker histones. FASEB J 2001; 15:34-42; PMID:11149891; http://dx.doi.org/10.1096/fj.00-0237rev
   PubMed Web of Science ®Google Scholar
• Gonzalez-Romero R, Rivera-Casas C, Frehlick LJ, Mendez J, Ausio J, Eirin-Lopez JM. Histone H2A (H2A.X and H2A.Z) variants in molluscs: molecular characterization and potential implications for chromatin dynamics. PLoS One 2012; 7:e30006; PMID:22253857; http://dx.doi.org/10.1371/journal.pone.0030006
   PubMedGoogle Scholar
• Eirin-Lopez JM, Gonzalez-Romero R, Dryhurst D, Ishibashi T, Ausio J. The evolutionary differentiation of two histone H2A.Z variants in chordates (H2A.Z-1 and H2A.Z-2) is mediated by a stepwise mutation process that affects three amino acid residues. BMC Evol Biol 2009; 9:31; PMID:19193230; http://dx.doi.org/10.1186/1471-2148-9-31
   PubMed Web of Science ®Google Scholar
• Eirin-Lopez JM, Ausio J. Origin and evolution of chromosomal sperm proteins. Bioessays 2009; 31:1062-70; PMID:19708021; http://dx.doi.org/10.1002/bies.200900050
   PubMedGoogle Scholar
• Lewis JD, Ausió J. Protamine-like proteins: evidence for a novel chromatin structure. Biochemistry and cell biology = Biochimie et biologie cellulaire 2002; 80:353-61; PMID:12123288; http://dx.doi.org/10.1139/o02-083
   PubMed Web of Science ®Google Scholar
• Avramova Z, Zalensky A, Tsanev R. Biochemical and ultrastructural study of the sperm chromatin from Mytilus galloprovincialis. Experimental cell research 1984; 152:231-9; PMID:6232144; http://dx.doi.org/10.1016/0014-4827(84)90248-9
   PubMed Web of Science ®Google Scholar
• Ishibashi T, Thambirajah AA, Ausio J. MeCP2 preferentially binds to methylated linker DNA in the absence of the terminal tail of histone H3 and independently of histone acetylation. FEBS letters 2008; 582:1157-62; PMID:18339321; http://dx.doi.org/10.1016/j.febslet.2008.03.005
   PubMed Web of Science ®Google Scholar
• Malik HS, Henikoff S. Phylogenomics of the nucleosome. Nat Struct Biol 2003; 10:882-91; PMID:14583738; http://dx.doi.org/10.1038/nsb996
   PubMedGoogle Scholar
• Talbert PB, Henikoff S. Histone variants–ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol 2010; 11:264-75; PMID:20197778; http://dx.doi.org/10.1038/nrm2861
   PubMed Web of Science ®Google Scholar
• Cheema MS, Ausio J. The Structural Determinants behind the Epigenetic Role of Histone Variants. Genes (Basel) 2015; 6:685-713; PMID:26213973; http://dx.doi.org/10.3390/genes6030685
   PubMed Web of Science ®Google Scholar
• Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 1997; 389:251-60; PMID:9305837; http://dx.doi.org/10.1038/38444
   PubMed Web of Science ®Google Scholar
• Ruiz-Trillo I, Roger AJ, Burger G, Gray MW, Lang BF. A phylogenomic investigation into the origin of metazoa. Mol Biol Evol 2008; 25:664-72; PMID:18184723; http://dx.doi.org/10.1093/molbev/msn006
   PubMed Web of Science ®Google Scholar
• Sebe-Pedros A, de Mendoza A, Lang BF, Degnan BM, Ruiz-Trillo I. Unexpected repertoire of metazoan transcription factors in the unicellular holozoan Capsaspora owczarzaki. Mol Biol Evol 2011; 28:1241-54; PMID:21087945; http://dx.doi.org/10.1093/molbev/msq309
   PubMed Web of Science ®Google Scholar
• Dryhurst D, Ishibashi T, Rose KL, Eirin-Lopez JM, McDonald D, Silva-Moreno B, Veldhoen N, Helbing CC, Hendzel MJ, Shabanowitz J, et al. Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates. BMC Biol 2009; 7:86; PMID:20003410; http://dx.doi.org/10.1186/1741-7007-7-86
   PubMed Web of Science ®Google Scholar
• Bonisch C, Schneider K, Punzeler S, Wiedemann SM, Bielmeier C, Bocola M, Eberl HC, Kuegel W, Neumann J, Kremmer E, et al. H2A.Z.2.2 is an alternatively spliced histone H2A.Z variant that causes severe nucleosome destabilization. Nucleic Acids Res 2012; 40(13):5951-64; PMID: 22467210; http://dx.doi.org/10.1093/nar/gks267
   PubMed Web of Science ®Google Scholar
• Turner JM, Mahadevaiah SK, Elliott DJ, Garchon HJ, Pehrson JR, Jaenisch R, Burgoyne PS. Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist. J Cell Sci 2002; 115:4097-105; PMID:12356914; http://dx.doi.org/10.1242/jcs.00111
   PubMed Web of Science ®Google Scholar
• Chang CC, Ma Y, Jacobs S, Tian XC, Yang X, Rasmussen TP. A maternal store of macroH2A is removed from pronuclei prior to onset of somatic macroH2A expression in preimplantation embryos. Dev Biol 2005; 278:367-80; PMID:15680357; http://dx.doi.org/10.1016/j.ydbio.2004.11.032
   PubMed Web of Science ®Google Scholar
• Castillo J, Amaral A, Azpiazu R, Vavouri T, Estanyol JM, Ballesca JL, Oliva R. Genomic and proteomic dissection and characterisation of the human sperm chromatin. Molecular human reproduction 2014; 20(11):1041-53; PMID:25193639; http://dx.doi.org/10.1093/molehr/gau079
   PubMed Web of Science ®Google Scholar
• Jemaa M, Morin N, Cavelier P, Cau J, Strub JM, Delsert C. Adult somatic progenitor cells and hematopoiesis in oysters. J Exp Biol 2014; 217:3067-77; PMID:24948634; http://dx.doi.org/10.1242/jeb.106575
   PubMed Web of Science ®Google Scholar
• Pasque V, Gillich A, Garrett N, Gurdon JB. Histone variant macroH2A confers resistance to nuclear reprogramming. Embo j 2011; 30:2373-87; PMID:21552206; http://dx.doi.org/10.1038/emboj.2011.144
   PubMed Web of Science ®Google Scholar
• Pasque V, Radzisheuskaya A, Gillich A, Halley-Stott RP, Panamarova M, Zernicka-Goetz M, Surani MA, Silva JC. Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency. J Cell Sci 2012; 125:6094-104; PMID:23077180; http://dx.doi.org/10.1242/jcs.113019
   PubMed Web of Science ®Google Scholar
• Barrero MJ, Sese B, Marti M, Izpisua Belmonte JC. Macro histone variants are critical for the differentiation of human pluripotent cells. J Biol Chem 2013; 288:16110-6; PMID:23595991; http://dx.doi.org/10.1074/jbc.M113.466144
   PubMed Web of Science ®Google Scholar
• Lewis JD, Abbott DW, Ausio J. A haploid affair: core histone transitions during spermatogenesis. Biochem Cell Biol 2003; 81:131-40; PMID:12897846; http://dx.doi.org/10.1139/o03-045
   PubMed Web of Science ®Google Scholar
• Mermoud JE, Tassin AM, Pehrson JR, Brockdorff N. Centrosomal association of histone macroH2A1.2 in embryonic stem cells and somatic cells. Exp Cell Res 2001; 268:245-51; PMID:11478850; http://dx.doi.org/10.1006/excr.2001.5277
   PubMed Web of Science ®Google Scholar
• Gamble MJ, Kraus WL. Multiple facets of the unique histone variant macroH2A: from genomics to cell biology. Cell Cycle 2010; 9:2568-74; PMID:20543561; http://dx.doi.org/10.4161/cc.9.13.12144
   PubMed Web of Science ®Google Scholar
• Maze I, Noh KM, Soshnev AA, Allis CD. Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nat Rev Genet 2014; 15:259-71; PMID:24614311; http://dx.doi.org/10.1038/nrg3673
   PubMed Web of Science ®Google Scholar
• Ausio J. Histone variants–the structure behind the function. Brief Funct Genomic Proteomic 2006; 5:228-43; PMID:16772274; http://dx.doi.org/10.1093/bfgp/ell020
   PubMedGoogle Scholar
• Suarez-Ulloa V, Fernandez-Tajes J, Aguiar-Pulido V, Rivera-Casas C, Gonzalez-Romero R, Ausio J, Mendez J, Dorado J, Eirin-Lopez JM. The CHROMEVALOA database: a resource for the evaluation of Okadaic Acid contamination in the marine environment based on the chromatin-associated transcriptome of the mussel Mytilus galloprovincialis. Mar Drugs 2013; 11:830-41; PMID:23481679; http://dx.doi.org/10.3390/md11030830
   PubMed Web of Science ®Google Scholar
• Marino-Ramirez L, Levine KM, Morales M, Zhang S, Moreland RT, Baxevanis AD, Landsman D. The Histone Database: an integrated resource for histones and histone fold-containing proteins. Database (Oxford) 2011; 2011:bar048.
   PubMed Web of Science ®Google Scholar
• Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW. GenBank. Nucleic Acids Res 2013; 41:D36-42; PMID:23193287; http://dx.doi.org/10.1093/nar/gks1195
   PubMed Web of Science ®Google Scholar
• Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symposium Series 1999; 41:95-8.
   Google Scholar
• Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol 2013; 30:2725-9; PMID:24132122; http://dx.doi.org/10.1093/molbev/mst197
   PubMed Web of Science ®Google Scholar
• Jones DT, Taylor WR, Thornton JM. The rapid generation of mutation data matrices from protein sequences. Comput Applic Biosci 1992; 8:275-82.
   PubMedGoogle Scholar
• Ausió J, Moore SC. Reconstitution of chromatin complexes from high-performance liquid chromatography-purified histones. Methods (San Diego, Calif) 1998; 15:333-42; PMID:9740721; http://dx.doi.org/10.1006/meth.1998.0637
   PubMed Web of Science ®Google Scholar
• Ishibashi T, Dryhurst D, Rose KL, Shabanowitz J, Hunt DF, Ausio J. Acetylation of vertebrate H2A.Z and its effect on the structure of the nucleosome. Biochemistry 2009; 48:5007-17; PMID:19385636; http://dx.doi.org/10.1021/bi900196c
   PubMed Web of Science ®Google Scholar
• Thambirajah AA, Ng MK, Frehlick LJ, Li A, Serpa JJ, Petrotchenko EV, Silva-Moreno B, Missiaen KK, Borchers CH, Adam Hall J, et al. MeCP2 binds to nucleosome free (linker DNA) regions and to H3K9/H3K27 methylated nucleosomes in the brain. Nucleic acids research 2011; 40:2884-97; PMID:22144686; http://dx.doi.org/10.1093/nar/gkr1066
   PubMed Web of Science ®Google Scholar
• Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nature protocols 2015; 10:845-58; PMID:25950237; http://dx.doi.org/10.1038/nprot.2015.053
   PubMed Web of Science ®Google Scholar