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HU DNA-binding transcriptional dual regulator

Synonyms: HU
Summary:
The HU protein is a small DNA-binding protein that is considered a global regulatory protein and shares properties with histones, which play an important role in nucleoid organization [8, 9, 10, 11] and regulation [1, 5, 7, 12, 13, 14]. The HU protein has been shown to be involved in DNA replication [15, 16, 17]and the formation of transcription foci [18] and it modulates the binding of IHF to oriC [19]and stabilizes the DnaA oligomer bound to oriC [20] As another example, HU is required for the expression of σS factors [21] Recently, Oberto et al.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
HU Functional   nd nd
TFBs length: 34
TFBs symmetry: inverted-repeat
Sensing class: TFs for DNA-bending
Connectivity class: Local Regulator
Gene name: hupA
  Genome position: 4200281-4200553
  Length: 273 bp / 90 aa
Operon name: hupA
TU(s) encoding the TF:
Transcription unit        Promoter
hupA
hupAp
Gene name: hupB
  Genome position: 461451-461723
  Length: 273 bp / 90 aa
Operon name: hupB
TU(s) encoding the TF:
Transcription unit        Promoter
hupB
hupBp1
hupB
hupBp2
hupB
hupBp3
hupB
hupBp4


Regulon       
Regulated gene(s) galE, galK, galM, galT, micF, mtr, pgm, seqA, tyrP
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (5)
colanic acid (M antigen) (3)
galactose metabolism (3)
capsule (M and K antigens) (3)
antisense RNA (2)
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Regulated operon(s) galETKM, micF, mtr, seqA-pgm, tyrP
First gene in the operon(s) galE, micF, mtr, seqA, tyrP
Simple and complex regulons AcrR,H-NS,HU,IHF,Lrp,MarA,OmpR,Rob,SoxS
CRP,GalR,GalS,H-NS,HU
CRP,GalR,GalS,HU
HU
HU,IHF,TrpR,TyrR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[HU,-](6)
[HU,+](2)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  HU repressor galEp Sigma38 6.5 -20.5 galE, galT, galK, galM
ttgttatgctATGGTTATTTCATACCATAAGCCTAATGGAGCGAattatgagag
792059 792092 [GEA], [BPP] [1], [2], [3], [4]
  HU repressor galEp1 Sigma70 6.5 -20.5 galE, galT, galK, galM
ttgttatgctATGGTTATTTCATACCATAAGCCTAATGGAGCGAattatgagag
792059 792092 [GEA], [BPP] [1], [2], [3], [4]
  HU repressor galEp2 Sigma70 6.5 -25.5 galE, galT, galK, galM
catctttgttATGCTATGGTTATTTCATACCATAAGCCTAATGGagcgaattat
792064 792097 [GEA], [BPP] [1], [2], [3], [4]
  HU activator micFp1 Sigma70 nd nd micF nd nd [GEA], [BPP] [5]
  HU activator micFp2 Sigma38 nd nd micF nd nd [GEA], [BPP] [5]
  HU repressor mtrp2 Sigma70 nd nd mtr nd nd [GEA], [BPP] [6]
  HU repressor seqAp nd nd nd seqA, pgm nd nd [GEA], [BPP] [7]
  HU repressor tyrPp1 Sigma70 nd nd tyrP nd nd [GEA], [BPP] [6]


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation




Reference(s)    

 [1] Aki T., Adhya S., 1997, Repressor induced site-specific binding of HU for transcriptional regulation., EMBO J 16(12):3666-74

 [2] Lia G., Bensimon D., Croquette V., Allemand JF., Dunlap D., Lewis DE., Adhya S., Finzi L., 2003, Supercoiling and denaturation in Gal repressor/heat unstable nucleoid protein (HU)-mediated DNA looping., Proc Natl Acad Sci U S A 100(20):11373-7

 [3] Lyubchenko YL., Shlyakhtenko LS., Aki T., Adhya S., 1997, Atomic force microscopic demonstration of DNA looping by GalR and HU., Nucleic Acids Res 25(4):873-6

 [4] Perez N., Rehault M., Amouyal M., 2000, A functional assay in Escherichia coli to detect non-assisted interaction between galactose repressor dimers., Nucleic Acids Res 28(18):3600-4

 [5] Painbeni E., Caroff M., Rouviere-Yaniv J., 1997, Alterations of the outer membrane composition in Escherichia coli lacking the histone-like protein HU., Proc Natl Acad Sci U S A 94(13):6712-7

 [6] Yang J., Camakaris H., Pittard AJ., 1996, In vitro transcriptional analysis of TyrR-mediated activation of the mtr and tyrP+3 promoters of Escherichia coli., J Bacteriol 178(21):6389-93

 [7] Lee H., Kim HK., Kang S., Hong CB., Yim J., Hwang DS., 2001, Expression of the seqA gene is negatively modulated by the HU protein in Escherichia coli., Mol Gen Genet 264(6):931-5

 [8] 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(20):6361 10.1128/JB.181.20.6361-6370.1999

 [9] Azam TA, Ishihama A, 1999, Twelve species of the nucleoid-associated protein from Escherichia coli. Sequence recognition specificity and DNA binding affinity., J Biol Chem, 274(46):33105 10.1074/jbc.274.46.33105

 [10] Azam TA., Hiraga S., Ishihama A., 2000, Two types of localization of the DNA-binding proteins within the Escherichia coli nucleoid., Genes Cells 5(8):613-26

 [11] Dorman CJ, 2009, Nucleoid-associated proteins and bacterial physiology., Adv Appl Microbiol, 67(None):47 10.1016/S0065-2164(08)01002-2

 [12] Kar S, Edgar R, Adhya S, 2005, Nucleoid remodeling by an altered HU protein: reorganization of the transcription program., Proc Natl Acad Sci U S A, 102(45):16397 10.1073/pnas.0508032102

 [13] 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(2):e4367 10.1371/journal.pone.0004367

 [14] Semsey S., Tolstorukov MY., Virnik K., Zhurkin VB., Adhya S., 2004, DNA trajectory in the Gal repressosome., Genes Dev 18(15):1898-907

 [15] Jaffe A., Vinella D., D'Ari R., 1997, The Escherichia coli histone-like protein HU affects DNA initiation, chromosome partitioning via MukB, and cell division via MinCDE., J Bacteriol 179(11):3494-9

 [16] Ryan VT, Grimwade JE, Nievera CJ, Leonard AC, 2002, IHF and HU stimulate assembly of pre-replication complexes at Escherichia coli oriC by two different mechanisms., Mol Microbiol, 46(1):113 10.1046/j.1365-2958.2002.03129.x

 [17] Kano Y, Ogawa T, Ogura T, Hiraga S, Okazaki T, Imamoto F, 1991, Participation of the histone-like protein HU and of IHF in minichromosomal maintenance in Escherichia coli., Gene, 103(1):25 10.1016/0378-1119(91)90386-p

 [18] Berger M, Farcas A, Geertz M, Zhelyazkova P, Brix K, Travers A, Muskhelishvili G, 2010, Coordination of genomic structure and transcription by the main bacterial nucleoid-associated protein HU., EMBO Rep, 11(1):59 10.1038/embor.2009.232

 [19] 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(12):4489 10.1002/j.1460-2075.1992.tb05550.x

 [20] Chodavarapu S, Felczak MM, Yaniv JR, Kaguni JM, 2008, Escherichia coli DnaA interacts with HU in initiation at the E. coli replication origin., Mol Microbiol, 67(4):781 10.1111/j.1365-2958.2007.06094.x

 [21] Balandina A, Claret L, Hengge-Aronis R, Rouviere-Yaniv J, 2001, The Escherichia coli histone-like protein HU regulates rpoS translation., Mol Microbiol, 39(4):1069 10.1046/j.1365-2958.2001.02305.x

 [22] Bi H, Sun L, Fukamachi T, Saito H, Kobayashi H, 2009, HU participates in expression of a specific set of genes required for growth and survival at acidic pH in Escherichia coli., Curr Microbiol, 58(5):443 10.1007/s00284-008-9340-4

 [23] Kano Y, Osato K, Wada M, Imamoto F, 1987, Cloning and sequencing of the HU-2 gene of Escherichia coli., Mol Gen Genet, 209(2):408 10.1007/BF00329674

 [24] Kano Y, Wada M, Imamoto F, 1988, Genetic characterization of the gene hupA encoding the HU-2 protein of Escherichia coli., Gene, 69(2):331 10.1016/0378-1119(88)90443-x

 [25] Laine B., Kmiecik D., Sautiere P., Biserte G., Cohen-Solal M., 1980, Complete amino-acid sequences of DNA-binding proteins HU-1 and HU-2 from Escherichia coli., Eur J Biochem 103(3):447-61

 [26] Kohno K., Wada M., Kano Y., Imamoto F., 1990, Promoters and autogenous control of the Escherichia coli hupA and hupB genes., J Mol Biol 213(1):27-36

 [27] 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(3):687 10.1002/j.1460-2075.1991.tb07998.x

 [28] Giangrossi M, Giuliodori AM, Gualerzi CO, Pon CL, 2002, Selective expression of the beta-subunit of nucleoid-associated protein HU during cold shock in Escherichia coli., Mol Microbiol, 44(1):205 10.1046/j.1365-2958.2002.02868.x

 [29] Bonnefoy E, Takahashi M, Yaniv JR, 1994, DNA-binding parameters of the HU protein of Escherichia coli to cruciform DNA., J Mol Biol, 242(2):116 10.1006/jmbi.1994.1563

 [30] Castaing B, Zelwer C, Laval J, Boiteux S, 1995, HU protein of Escherichia coli binds specifically to DNA that contains single-strand breaks or gaps., J Biol Chem, 270(17):10291 10.1074/jbc.270.17.10291

 [31] Lavoie BD, Shaw GS, Millner A, Chaconas G, 1996, Anatomy of a flexer-DNA complex inside a higher-order transposition intermediate., Cell, 85(5):761 10.1016/s0092-8674(00)81241-6

 [32] Pontiggia A, Negri A, Beltrame M, Bianchi ME, 1993, Protein HU binds specifically to kinked DNA., Mol Microbiol, 7(3):343 10.1111/j.1365-2958.1993.tb01126.x

 [33] 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(1):101 10.1016/s0022-2836(03)00725-3

 [34] Garnier N, Loth K, Coste F, Augustyniak R, Nadan V, Damblon C, Castaing B, 2011, An alternative flexible conformation of the E. coli HU?? protein: structural, dynamics, and functional aspects., Eur Biophys J, 40(2):117 10.1007/s00249-010-0630-y

 [35] Le Meur R, Loth K, Culard F, Castaing B, Landon C, 2015, Backbone assignment of the three dimers of HU from Escherichia coli at 293 K: EcHU?2, EcHU?2 and EcHU??., Biomol NMR Assign, 9(2):359 10.1007/s12104-015-9610-6

 [36] Arora K, Thakur B, Mrigwani A, Guptasarma P, 2021, N-Terminal Extensions Appear to Frustrate HU Heterodimer Formation by Strengthening Intersubunit Contacts and Blocking the Formation of a Heterotetrameric Intermediate., Biochemistry, 60(23):1836 10.1021/acs.biochem.1c00081

 [37] Guo F, Adhya S, 2007, Spiral structure of Escherichia coli HUalphabeta provides foundation for DNA supercoiling., Proc Natl Acad Sci U S A, 104(11):4309 10.1073/pnas.0611686104

 [38] Kuroda A, Nomura K, Takiguchi N, Kato J, Ohtake H, 2006, Inorganic polyphosphate stimulates lon-mediated proteolysis of nucleoid proteins in Escherichia coli., Cell Mol Biol (Noisy-le-grand), 52(4):23 None

 [39] Longo F., Motta S., Mauri P., Landini P., Rossi E., 2016, Interplay of the modified nucleotide phosphoadenosine 5'-phosphosulfate (PAPS) with global regulatory proteins in Escherichia coli: modulation of cyclic AMP (cAMP)-dependent gene expression and interaction with the HupA regulatory protein., Chem Biol Interact 259(Pt A):39-47

 [40] Dilweg IW, Dame RT, 2018, Post-translational modification of nucleoid-associated proteins: an extra layer of functional modulation in bacteria?, Biochem Soc Trans, 46(5):1381 10.1042/BST20180488

 [41] Niccum BA., Lee H., MohammedIsmail W., Tang H., Foster PL., 2019, The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the Escherichia coli Chromosome Has Multiple Causes., MBio 10(4)

 [42] Dame RT., Goosen N., 2002, HU: promoting or counteracting DNA compaction?, FEBS Lett 529(2-3):151-6

 [43] Sarkar T, Vitoc I, Mukerji I, Hud NV, 2007, Bacterial protein HU dictates the morphology of DNA condensates produced by crowding agents and polyamines., Nucleic Acids Res, 35(3):951 10.1093/nar/gkl1093

 [44] Boubrik F, Bonnefoy E, Rouvière-Yaniv J, 1991, HU and IHF: similarities and differences. In Escherichia coli, the lack of HU is not compensated for by IHF., Res Microbiol, 142(2-3):239 10.1016/0923-2508(91)90036-a

 [45] Rouvière-Yaniv J, Yaniv M, Germond JE, 1979, E. coli DNA binding protein HU forms nucleosomelike structure with circular double-stranded DNA., Cell, 17(2):265 10.1016/0092-8674(79)90152-1

 [46] Shindo H, Furubayashi A, Shimizu M, Miyake M, Imamoto F, 1992, Preferential binding of E.coli histone-like protein HU alpha to negatively supercoiled DNA., Nucleic Acids Res, 20(7):1553 10.1093/nar/20.7.1553

 [47] Yan Y, Leng F, Finzi L, Dunlap D, 2018, Protein-mediated looping of DNA under tension requires supercoiling., Nucleic Acids Res, 46(5):2370 10.1093/nar/gky021

 [48] Huang L, Zhang Z, McMacken R, 2021, Interaction of the Escherichia coli HU Protein with Various Topological Forms of DNA., Biomolecules, 11(11):None 10.3390/biom11111724

 [49] Remesh SG, Verma SC, Chen JH, Ekman AA, Larabell CA, Adhya S, Hammel M, 2020, Nucleoid remodeling during environmental adaptation is regulated by HU-dependent DNA bundling., Nat Commun, 11(1):2905 10.1038/s41467-020-16724-5

 [50] Japaridze A, Muskhelishvili G, Benedetti F, Gavriilidou AF, Zenobi R, De Los Rios P, Longo G, Dietler G, 2017, Hyperplectonemes: A Higher Order Compact and Dynamic DNA Self-Organization., Nano Lett, 17(3):1938 10.1021/acs.nanolett.6b05294

 [51] Kamashev D, Balandina A, Rouviere-Yaniv J, 1999, The binding motif recognized by HU on both nicked and cruciform DNA., EMBO J, 18(19):5434 10.1093/emboj/18.19.5434

 [52] Krolenko EV, Kamashev DE, Balandina AV, Karpov VL, Rouviere-Yaniv J, Preobrazhenskaia OV, 1999, [Immunochemical detection of the histone-like bacterial protein Hu in covalently bound DNA-protein complexes, obtained in vitro and in vivo]., Mol Biol (Mosk), 33(3):442 None

 [53] Czapla L, Swigon D, Olson WK, 2008, Effects of the nucleoid protein HU on the structure, flexibility, and ring-closure properties of DNA deduced from Monte Carlo simulations., J Mol Biol, 382(2):353 10.1016/j.jmb.2008.05.088

 [54] Xiao B, Zhang H, Johnson RC, Marko JF, 2011, Force-driven unbinding of proteins HU and Fis from DNA quantified using a thermodynamic Maxwell relation., Nucleic Acids Res, 39(13):5568 10.1093/nar/gkr141

 [55] Lin SN, Dame RT, Wuite GJL, 2021, Direct visualization of the effect of DNA structure and ionic conditions on HU-DNA interactions., Sci Rep, 11(1):18492 10.1038/s41598-021-97763-w

 [56] Kamashev D, Agapova Y, Rastorguev S, Talyzina AA, Boyko KM, Korzhenevskiy DA, Vlaskina A, Vasilov R, Timofeev VI, Rakitina TV, 2017, Comparison of histone-like HU protein DNA-binding properties and HU/IHF protein sequence alignment., PLoS One, 12(11):e0188037 10.1371/journal.pone.0188037

 [57] Czapla L, Peters JP, Rueter EM, Olson WK, Maher LJ, 2011, Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins., J Mol Biol, 409(2):278 10.1016/j.jmb.2011.03.050

 [58] Stracy M, Schweizer J, Sherratt DJ, Kapanidis AN, Uphoff S, Lesterlin C, 2021, Transient non-specific DNA binding dominates the target search of bacterial DNA-binding proteins., Mol Cell, 81(7):1499 10.1016/j.molcel.2021.01.039

 [59] Tan C, Terakawa T, Takada S, 2016, Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics., J Am Chem Soc, 138(27):8512 10.1021/jacs.6b03729

 [60] Mohapatra S, Weisshaar JC, 2018, Modified Pearson correlation coefficient for two-color imaging in spherocylindrical cells., BMC Bioinformatics, 19(1):428 10.1186/s12859-018-2444-3

 [61] Walker DM, Freddolino PL, Harshey RM, 2020, A Well-Mixed E. coli Genome: Widespread Contacts Revealed by Tracking Mu Transposition., Cell, 180(4):703 10.1016/j.cell.2020.01.031

 [62] Thakur B, Arora K, Gupta A, Guptasarma P, 2021, The DNA-binding protein HU is a molecular glue that attaches bacteria to extracellular DNA in biofilms., J Biol Chem, 296(None):100532 10.1016/j.jbc.2021.100532

 [63] Yao Y, Ma Y, Chen X, Bade R, Lv C, Zhu R, 2018, Absence of RstA results in delayed initiation of DNA replication in Escherichia coli., PLoS One, 13(7):e0200688 10.1371/journal.pone.0200688

 [64] Macvanin M, Adhya S, 2012, Architectural organization in E. coli nucleoid., Biochim Biophys Acta, 1819(7):830 10.1016/j.bbagrm.2012.02.012



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