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Nucleoid-Associated Protein HU: A Lilliputian in Gene Regulation of Bacterial Virulence

. 2019 ; 9 () : 159. [epub] 20190510

Language English Country Switzerland Media electronic-ecollection

Document type Journal Article, Research Support, Non-U.S. Gov't, Review

Nucleoid-associated proteins belong to a group of small but abundant proteins in bacterial cells. These transcription regulators are responsible for many important cellular processes and also are involved in pathogenesis of bacteria. The best-known nucleoid-associated proteins, such as HU, FIS, H-NS, and IHF, are often discussed. The most important findings in research concerning HU protein are described in this mini review. Its roles in DNA compaction, shape modulation, and negative supercoiling induction have been studied intensively. HU protein regulates bacteria survival, growth, SOS response, virulence genes expression, cell division, and many other cell processes. Elucidating the mechanism of HU protein action has been the subject of many research projects. This mini review provides a comprehensive overview of the HU protein.

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Aki T., Choy H. E., Adhya S. (1996). Histone-like protein HU as a specific transcriptional regulator: co-factor role in repression of gal transcription by GAL repressor. Genes Cells Devoted Mol. Cell. Mech. 1, 179–188. 10.1046/j.1365-2443.1996.d01-236.x PubMed DOI

Ali Azam T., Iwata A., Nishimura A., Ueda S., Ishihama A. (1999). Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. J. Bacteriol. 181, 6361–6370. PubMed PMC

Anand C., Garg R., Ghosh S., Nagaraja V. (2017). A Sir2 family protein Rv1151c deacetylates HU to alter its DNA binding mode in Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 493, 1204–1209. 10.1016/j.bbrc.2017.09.087 PubMed DOI

Azam T. A., Ishihama A. (1999). Twelve species of the nucleoid-associated protein from Escherichia coli. Sequence recognition specificity and DNA binding affinity. J. Biol. Chem. 274, 33105–33113. 10.1074/jbc.274.46.33105 PubMed DOI

Bahloul A., Boubrik F., Rouviere-Yaniv J. (2001). Roles of Escherichia coli histone-like protein HU in DNA replication:HU-beta suppresses the thermosensitivity of dnaA46ts. Biochimie 83, 219–229. 10.1016/S0300-9084(01)01246-9 PubMed DOI

Balandina A., Claret L., Hengge-Aronis R., Rouviere-Yaniv J. (2001). The Escherichia coli histone-like protein HU regulates rpoS translation. Mol. Microbiol. 39, 1069–1079. 10.1046/j.1365-2958.2001.02305.x PubMed DOI

Balandina A., Kamashev D., Rouviere-Yaniv J. (2002). The bacterial histone-like protein HU specifically recognizes similar structures in all nucleic acids DNA, RNA, and their hybrids. J. Biol. Chem. 277, 27622–27628. 10.1074/jbc.M201978200 PubMed DOI

Becker N. A., Kahn J. D., Maher L. J. (2005). Bacterial repression loops require enhanced DNA flexibility. J. Mol. Biol. 349, 716–730. 10.1016/j.jmb.2005.04.035 PubMed DOI

Berger M., Gerganova V., Berger P., Rapiteanu R., Lisicovas V., Dobrindt U. (2016). Genes on a wire: the nucleoid-associated protein HU insulates transcription units in Escherichia coli. Sci. Rep. 6:31512. 10.1038/srep31512 PubMed DOI PMC

Bhowmick T., Ghosh S., Dixit K., Ganesan V., Ramagopal U. A., Dey D., et al. . (2014). Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors. Nat. Commun. 5:4124. 10.1038/ncomms5124 PubMed DOI

Bonnefoy E., Rouvière-Yaniv J. (1991). HU and IHF, two homologous histone-like proteins of Escherichia coli, form different protein-DNA complexes with short DNA fragments. EMBO J. 10, 687–696. 10.1002/j.1460-2075.1991.tb07998.x PubMed DOI PMC

Bonnefoy E., Rouvière-Yaniv J. (1992). HU, the major histone-like protein of E. coli, modulates the binding of IHF to oriC. EMBO J. 11, 4489–4496. 10.1002/j.1460-2075.1992.tb05550.x PubMed DOI PMC

Boubrik F., Rouviere-Yaniv J. (1995). Increased sensitivity to gamma irradiation in bacteria lacking protein HU. Proc. Natl. Acad. Sci. U.S.A. 92, 3958–3962. 10.1073/pnas.92.9.3958 PubMed DOI PMC

Boyko K. M., Rakitina T. V., Korzhenevskiy D. A., Vlaskina A. V., Agapova Y. K., Kamashev D. E., et al. . (2016). Structural basis of the high thermal stability of the histone-like HU protein from the mollicute Spiroplasma melliferum KC3. Sci. Rep. 6:36366. 10.1038/srep36366 PubMed DOI PMC

Broyles S. S., Pettijohn D. E. (1986). Interaction of the Escherichia coli HU protein with DNA. Evidence for formation of nucleosome-like structures with altered DNA helical pitch. J. Mol. Biol. 187, 47–60. 10.1016/0022-2836(86)90405-5 PubMed DOI

Chen C., Ghosh S., Grove A. (2004). Substrate specificity of Helicobacter pylori histone-like HU protein is determined by insufficient stabilization of DNA flexure points. Biochem. J. 383, 343–351. 10.1042/BJ20040938 PubMed DOI PMC

Christodoulou E., Rypniewski W. R., Vorgias C. R. E. (2003). High-resolution X-ray structure of the DNA-binding protein HU from the hyper-thermophilic Thermotoga maritima and the determinants of its thermostability. Extrem. Life Extreme Cond. 7, 111–122. 10.1007/s00792-002-0302-7 PubMed DOI

Christodoulou E., Vorgias C. E. (1998). Cloning, overproduction, purification and crystallization of the DNA binding protein HU from the hyperthermophilic eubacterium Thermotoga maritima. Acta Crystallogr. D Biol. Crystallogr. 54, 1043–1045. 10.1107/S0907444998000341 PubMed DOI

Conforte V. P., Malamud F., Yaryura P. M., Terrones L. T., Torres P. S., Pino V. D., et al. . (2018). The histone-like protein HupB influences biofilm formation and virulence in Xanthomonas citri ssp. citri through the regulation of flagellar biosynthesis. Mol. Plant Pathol. 20, 589–598. 10.1111/mpp.12777 PubMed DOI PMC

Dillon S. C., Dorman C. J. (2010). Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat. Rev. Microbiol. 8, 185–195. 10.1038/nrmicro2261 PubMed DOI

Dorman C. J. (2014). Function of nucleoid-associated proteins in chromosome structuring and transcriptional regulation. J. Mol. Microbiol. Biotechnol. 24, 316–331. 10.1159/000368850 PubMed DOI

Drlica K., Rouviere-Yaniv J. (1987). Histonelike proteins of bacteria. Microbiol. Rev. 51, 301–319. PubMed PMC

Ferrándiz M.-J., Carreño D., Ayora S., de la Campa A. G. (2018). HU of Streptococcus pneumoniae is essential for the preservation of DNA supercoiling. Front. Microbiol. 9:493. 10.3389/fmicb.2018.00493 PubMed DOI PMC

Floc'h K., Lacroix F., Servant P., Wong Y.-S., Kleman J.-P., Bourgeois D., et al. (2019). Cell morphology and nucleoid dynamics in dividing D. radiodurans. BioRxiv 582304 10.1101/582304 PubMed DOI PMC

Geanacopoulos M., Vasmatzis G., Zhurkin V. B., Adhya S. (2001). Gal repressosome contains an antiparallel DNA loop. Nat. Struct. Biol. 8, 432–436. 10.1038/87595 PubMed DOI

Ghosh S., Padmanabhan B., Anand C., Nagaraja V. (2016). Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization. Mol. Microbiol. 100, 577–588. 10.1111/mmi.13339 PubMed DOI

Grove A., Saavedra T. C. (2002). The role of surface-exposed lysines in wrapping DNA about the bacterial histone-like protein HU. Biochemistry 41, 7597–7603. 10.1021/bi016095e PubMed DOI

Guan Z., Wang Y., Gao L., Zhang W., Lu X. (2018). Effects of the histone-like protein HU on cellulose degradation and biofilm formation of Cytophaga hutchinsonii. Appl. Microbiol. Biotechnol. 102, 6593–6611. 10.1007/s00253-018-9071-9 PubMed DOI

Guo F., Adhya S. (2007). Spiral structure of Escherichia coli HUalphabeta provides foundation for DNA supercoiling. Proc. Natl. Acad. Sci. U.S.A. 104, 4309–4314. 10.1073/pnas.0611686104 PubMed DOI PMC

Gupta M., Sajid A., Sharma K., Ghosh S., Arora G., Singh R., et al. . (2014). HupB, a nucleoid-associated protein of Mycobacterium tuberculosis, is modified by serine/threonine protein kinases in vivo. J. Bacteriol. 196, 2646–2657. 10.1128/JB.01625-14 PubMed DOI PMC

Hołówka J., Trojanowski D., Ginda K., Wojtaś B., Gielniewski B., Jakimowicz D., et al. . (2017). HupB is a bacterial nucleoid-associated protein with an indispensable eukaryotic-like tail. MBio 8, e01272–e01217. 10.1128/mBio.01272-17 PubMed DOI PMC

Kamashev D., Agapova Y., Rastorguev S., Talyzina A. A., Boyko K. M., Korzhenevskiy D. A., et al. . (2017). Comparison of histone-like HU protein DNA-binding properties and HU/IHF protein sequence alignment. PLOS ONE 12:e0188037. 10.1371/journal.pone.0188037 PubMed DOI PMC

Kamashev D., Balandina A., Rouviere-Yaniv J. (1999). The binding motif recognized by HU on both nicked and cruciform DNA. EMBO J. 18, 5434–5444. 10.1093/emboj/18.19.5434 PubMed DOI PMC

Kamashev D., Rouviere-Yaniv J. (2000). The histone-like protein HU binds specifically to DNA recombination and repair intermediates. EMBO J. 19, 6527–6535. 10.1093/emboj/19.23.6527 PubMed DOI PMC

Kar S., Adhya S. (2001). Recruitment of HU by piggyback: a special role of GalR in repressosome assembly. Genes Dev. 15, 2273–2281. 10.1101/gad.920301 PubMed DOI PMC

Kawamura S., Abe Y., Ueda T., Masumoto K., Imoto T., Yamasaki N., et al. . (1998). Investigation of the structural basis for thermostability of DNA-binding protein HU from Bacillus stearothermophilus. J. Biol. Chem. 273, 19982–19987. 10.1074/jbc.273.32.19982 PubMed DOI

Kim D. H., Im H., Jee J. G., Jang S. B., Yoon H. J., Kwon A. R., et al. . (2014). β-Arm flexibility of HU from Staphylococcus aureus dictates the DNA-binding and recognition mechanism. Acta Crystallogr. D Biol. Crystallogr. 70, 3273–3289. 10.1107/S1399004714023931 PubMed DOI

Koli P., Sudan S., Fitzgerald D., Adhya S., Kar S. (2011). Conversion of commensal Escherichia coli K-12 to an invasive form via expression of a mutant histone-like protein. MBio 2, e00182–e00111. 10.1128/mBio.00263-11 PubMed DOI PMC

Krylov A. S., Zasedateleva O. A., Prokopenko D. V., Rouviere-Yaniv J., Mirzabekov A. D. (2001). Massive parallel analysis of the binding specificity of histone-like protein HU to single- and double-stranded DNA with generic oligodeoxyribonucleotide microchips. Nucleic Acids Res. 29, 2654–2660. 10.1093/nar/29.12.2654 PubMed DOI PMC

Lavoie B. D., Shaw G. S., Millner A., Chaconas G. (1996). Anatomy of a flexer-DNA complex inside a higher-order transposition intermediate. Cell 85, 761–771. 10.1016/S0092-8674(00)81241-6 PubMed DOI

Lease R. A., Belfort M. (2000). A trans-acting RNA as a control switch in Escherichia coli: DsrA modulates function by forming alternative structures. Proc. Natl. Acad. Sci. U.S.A. 97, 9919–9924. 10.1073/pnas.170281497 PubMed DOI PMC

Li S., Waters R. (1998). Escherichia coli strains lacking protein HU are UV sensitive due to a role for HU in homologous recombination. J. Bacteriol. 180, 3750–3756. PubMed PMC

Majdalani N., Cunning C., Sledjeski D., Elliott T., Gottesman S. (1998). DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription. Proc. Natl. Acad. Sci. U.S.A. 95, 12462–12467. 10.1073/pnas.95.21.12462 PubMed DOI PMC

Mangan M. W., Lucchini S., O Croinin T., Fitzgerald S., Hinton J. C. D., Dorman CJ. (2011). Nucleoid-associated protein HU controls three regulons that coordinate virulence, response to stress and general physiology in Salmonella enterica serovar Typhimurium. Microbiology 157, 1075–1087. 10.1099/mic.0.046359-0 PubMed DOI

Nakamura K., Yahagi S., Yamazaki T., Yamane K. (1999). Bacillus subtilis histone-like protein, HBsu, is an integral component of a SRP-like particle that can bind the Alu domain of small cytoplasmic RNA. J. Biol. Chem. 274, 13569–13576. 10.1074/jbc.274.19.13569 PubMed DOI

Oberto J., Nabti S., Jooste V., Mignot H., Rouviere-Yaniv J. (2009). The HU regulon is composed of genes responding to anaerobiosis, acid stress, high osmolarity and SOS induction. PLoS ONE 4:e4367. 10.1371/journal.pone.0004367 PubMed DOI PMC

Oliveira Paiva A. M., Friggen A. H., Qin L., Douwes R., Dame R. T., Smits W. K. (2019). The bacterial chromatin protein HupA can remodel DNA and associates with the nucleoid in Clostridium difficile. J. Mol. Biol. 431, 653–672. 10.1016/j.jmb.2019.01.001 PubMed DOI

Paino A., Lohermaa E., Sormunen R., Tuominen H., Korhonen J., Pöllänen M. T., et al. . (2012). Interleukin-1β is internalised by viable Aggregatibacter actinomycetemcomitans biofilm and locates to the outer edges of nucleoids. Cytokine 60, 565–574. 10.1016/j.cyto.2012.07.024 PubMed DOI

Pettijohn D. E. (1988). Histone-like proteins and bacterial chromosome structure. J. Biol. Chem. 263, 12793–12796. PubMed

Phan N. Q., Uebanso T., Shimohata T., Nakahashi M., Mawatari K., Takahashi A. (2015). DNA-binding protein HU coordinates pathogenicity in Vibrio parahaemolyticus. J. Bacteriol. 197, 2958–2964. 10.1128/JB.00306-15 PubMed DOI PMC

Preobrajenskaya O., Boullard A., Boubrik F., Schnarr M., Rouvière-Yaniv J. (1994). The protein HU can displace the LexA repressor from its DNA-binding sites. Mol. Microbiol. 13, 459–467. 10.1111/j.1365-2958.1994.tb00440.x PubMed DOI

Prieto A. I., Kahramanoglou C., Ali R. M., Fraser G. M., Seshasayee A. S. N., Luscombe N. M. (2012). Genomic analysis of DNA binding and gene regulation by homologous nucleoid-associated proteins IHF and HU in Escherichia coli K12. Nucleic Acids Res. 40, 3524–3537. 10.1093/nar/gkr1236 PubMed DOI PMC

Priyadarshini R., Cugini C., Arndt A., Chen T., Tjokro N. O., Goodman S. D., et al. . (2013). The nucleoid-associated protein HUβ affects global gene expression in Porphyromonas gingivalis. Microbiology 159, 219–229. 10.1099/mic.0.061002-0 PubMed DOI PMC

Ramstein J., Hervouet N., Coste F., Zelwer C., Oberto J., Castaing B. (2003). Evidence of a thermal unfolding dimeric intermediate for the Escherichia coli histone-like HU proteins: thermodynamics and structure. J. Mol. Biol. 331, 101–121. 10.1016/S0022-2836(03)00725-3 PubMed DOI

Rice P. A., Yang S., Mizuuchi K., Nash H. A. (1996). Crystal structure of an IHF-DNA complex: a protein-induced DNA U-turn. Cell 87, 1295–1306. 10.1016/S0092-8674(00)81824-3 PubMed DOI

Rouvière-Yaniv J., Gros F. (1975). Characterization of a novel, low-molecular-weight DNA-binding protein from Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 72, 3428–3432. 10.1073/pnas.72.9.3428 PubMed DOI PMC

Rouvière-Yaniv J., Gros F., Haselkorn R., Reiss C. (1977). Histone-Like Proteins in Prokaryotic Organisms and Their Interaction With DNA (New York, NY: Academic Press; ), 211–231.

Rouvière-Yaniv J., Yaniv M., Germond J. E. (1979). E. coli DNA binding protein HU forms nucleosomelike structure with circular double-stranded DNA. Cell 17, 265–274. 10.1016/0092-8674(79)90152-1 PubMed DOI

Roy S., Dimitriadis E. K., Kar S., Geanacopoulos M., Lewis M. S., Adhya S. (2005). Gal repressor-operator-HU ternary complex: pathway of repressosome formation. Biochemistry 44, 5373–5380. 10.1021/bi047720t PubMed DOI

Ryan V. T., Grimwade J. E., Nievera C. J., Leonard A. C. (2002). IHF and HU stimulate assembly of pre-replication complexes at Escherichia coli oriC by two different mechanisms. Mol. Microbiol. 46, 113–124. 10.1046/j.1365-2958.2002.03129.x PubMed DOI

Saitoh F., Kawamura S., Yamasaki N., Tanaka I., Kimura M. (1999). Arginine-55 in the beta-arm is essential for the activity of DNA-binding protein HU from Bacillus stearothermophilus. Biosci. Biotechnol. Biochem. 63, 2232–2235. 10.1271/bbb.63.2232 PubMed DOI

Sakatos A., Babunovic G. H., Chase M. R., Dills A., Leszyk J., Rosebrock T., et al. . (2018). Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria. Sci. Adv. 4:eaao1478. 10.1126/sciadv.aao1478 PubMed DOI PMC

Serban D., Arcineigas S. F., Vorgias C. E., Thomas G. J. (2003). Structure and dynamics of the DNA-binding protein HU of B. stearothermophilus investigated by Raman and ultraviolet-resonance Raman spectroscopy. Protein Sci. Publ. Protein Soc. 12, 861–870. 10.1110/ps.0234103 PubMed DOI PMC

Stojkova P., Spidlova P., Lenco J., Rehulkova H., Kratka L., Stulik J. (2018). HU protein is involved in intracellular growth and full virulence of Francisella tularensis. Virulence 9, 754–770. 10.1080/21505594.2018.1441588 PubMed DOI PMC

Swinger K. K., Lemberg K. M., Zhang Y., Rice P. A. (2003). Flexible DNA bending in HU-DNA cocrystal structures. EMBO J. 22, 3749–3760. 10.1093/emboj/cdg351 PubMed DOI PMC

Swinger K. K., Rice P. A. (2004). IHF and HU: flexible architects of bent DNA. Curr. Opin. Struct. Biol. 14, 28–35. 10.1016/j.sbi.2003.12.003 PubMed DOI

Swinger K. K., Rice P. A. (2007). Structure-based analysis of HU–DNA binding. J. Mol. Biol. 365, 1005–1016. 10.1016/j.jmb.2006.10.024 PubMed DOI PMC

Weinert B. T., Iesmantavicius V., Wagner S. A., Schölz C., Gummesson B., Beli P., et al. . (2013a). Acetyl-phosphate is a critical determinant of lysine acetylation in E. coli. Mol. Cell 51, 265–272. 10.1016/j.molcel.2013.06.003 PubMed DOI

Weinert B. T., Schölz C., Wagner S. A., Iesmantavicius V., Su D., Daniel J. A., et al. . (2013b). Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Rep. 4, 842–851. 10.1016/j.celrep.2013.07.024 PubMed DOI

Welfle H., Misselwitz R., Welfle K., Groch N., Heinemann U. (1992). Salt-dependent and protein-concentration-dependent changes in the solution structure of the DNA-binding histone-like protein, HBsu, from Bacillus subtilis. Eur. J. Biochem. 204, 1049–1055. 10.1111/j.1432-1033.1992.tb16727.x PubMed DOI

White S. W., Wilson K. S., Appelt K., Tanaka I. (1999). The high-resolution structure of DNA-binding protein HU from Bacillus stearothermophilus. Acta Crystallogr. D Biol. Crystallogr. 55, 801–809. 10.1107/S0907444999000578 PubMed DOI

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