RegulonDB RegulonDB 9.2:Regulon Page

HU DNA-binding transcriptional dual regulator

Synonyms: HU
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 [11, 12, 13, 14] and regulation [1, 7, 8, 10, 15, 16].
HU is a heterodimer formed by an α-subunit and a β-subunit, which are encoded by the hupA and hupB genes, respectively [17, 18, 19, 20, 21] and are differentially stimulated during cold shock [22] HU is a transcriptional dual regulator. HU-1 (HupB) and HU-2 (HupA) are closely related but differ by 28 residues, and they have a high content of hydrophobic residues represented mostly by alanine. There is no sequence homology between the proteins HU-1 and HU-2 compared to any of the five histones of different eukaryotes studied [19]
HU forms high-affinity complexes with DNA containing sharp bends, kinks, branched and bulged structures, or single-strand breaks and loops [5, 23, 24, 25, 26]
Three dimeric forms of HU exist in Escherichia coli: two homodimers, EcHUα2 and EcHUβ2, and a heterodimer, HUαβ [27] All these forms are in thermal equilibrium between two dimeric conformations (N2<-->I2) that vary in their secondary structure content [28] Based on NMR spectroscopy, it was revealed that the hupA and hupB genes code for the EcHUα and EcHUβ polypeptide chains, respectively (70% identity, 90% homology) [29].

Based on high-temperature molecular dynamics simulation and NMR experiments, information has been obtained about the structural and dynamic features at the atomic level for the N2<-->I2 thermal transition of the EcHUβ2 homodimer [28] A 3D model has been proposed for the major I2 conformation of EcHUβ2 [28]
The crystal structure of the DNA-HUαβ complex has been resolved [30] In the presence of poly(P), HupA is efficiently degraded by Lon [31] The presence of HU depends on the phase of growth [11] and it is distributed uniformly in the nucleoid [13] Currently, no inducer for this regulator has been reported in the literature.
Read more >

Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
HU     nd nd
Evolutionary Family: IHF
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
Gene name: hupB
  Genome position: 461451-461723
  Length: 273 bp / 90 aa
Operon name: hupB
TU(s) encoding the TF:
Transcription unit        Promoter

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)
Read more >
Regulated operon(s) galETKM, micF, mtr, seqA-pgm, tyrP
First gene in the operon(s) galE, galE, galE, galE, galE, galE, galE, galE, micF, mtr, seqA, tyrP
Simple and complex regulons AcrR,H-NS,HU,IHF,Lrp,MarA,OmpR,Rob,SoxS
Read more >
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

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 galEp1 Sigma70 6.5 -20.5 galE, galT, galK, galM
792059 792092 [BPP], [GEA] [1], [2], [3], [4], [5], [6], [7]
  HU repressor galEp2 Sigma70 6.5 -25.5 galE, galT, galK, galM
792064 792097 [BPP], [GEA] [1], [2], [4], [5], [6], [7]
  HU activator micFp Sigma70 nd nd micF nd nd [GEA] [8]
  HU repressor mtrp2 Sigma70 nd nd mtr nd nd [GEA] [9]
  HU repressor seqAp nd nd nd seqA, pgm nd nd [GEA] [10]
  HU repressor tyrPp1 Sigma70 nd nd tyrP nd nd [GEA] [9]

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


 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis


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

 [2] Geanacopoulos M., Vasmatzis G., Zhurkin VB., Adhya S., 2001, Gal repressosome contains an antiparallel DNA loop., Nat Struct Biol. 8(5):432-6

 [3] Lewis DE., Geanacopoulos M., Adhya S., 1999, Role of HU and DNA supercoiling in transcription repression: specialized nucleoprotein repression complex at gal promoters in Escherichia coli., Mol Microbiol. 31(2):451-61

 [4] 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

 [5] 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

 [6] 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

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

 [8] 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

 [9] 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

 [10] 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

 [11] 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):6361-70

 [12] 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):33105-13

 [13] 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

 [14] Dorman CJ., 2009, Nucleoid-associated proteins and bacterial physiology., Adv Appl Microbiol. 67:47-64

 [15] 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):16397-402

 [16] 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

 [17] 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

 [18] Kano Y., Wada M., Imamoto F., 1988, Genetic characterization of the gene hupA encoding the HU-2 protein of Escherichia coli., Gene. 69(2):331-5

 [19] 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

 [20] 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

 [21] Bonnefoy E., Rouviere-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):687-96

 [22] 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):205-16

 [23] 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):116-29

 [24] 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):10291-6

 [25] Lavoie BD., Shaw GS., Millner A., Chaconas G., 1996, Anatomy of a flexer-DNA complex inside a higher-order transposition intermediate., Cell. 85(5):761-71

 [26] Pontiggia A., Negri A., Beltrame M., Bianchi ME., 1993, Protein HU binds specifically to kinked DNA., Mol Microbiol. 7(3):343-50

 [27] 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):101-21

 [28] Garnier N., Loth K., Coste F., Augustyniak R., Nadan V., Damblon C., Castaing B., 2011, An alternative flexible conformation of the E. coli HU¿¿(2) protein: structural, dynamics, and functional aspects., Eur Biophys J. 40(2):117-29

 [29] 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):359-63

 [30] 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):4309-14

 [31] 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):23-9

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

 [33] 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):951-61

 [34] Boubrik F., Bonnefoy E., Rouviere-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):239-47

 [35] Rouviere-Yaniv J., Yaniv M., Germond JE., 1979, E. coli DNA binding protein HU forms nucleosomelike structure with circular double-stranded DNA., Cell. 17(2):265-74

 [36] 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):1553-8

 [37] 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

 [38] 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):113-24

 [39] 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):25-30

 [40] 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):59-64

 [41] Bonnefoy E., Rouviere-Yaniv J., 1992, HU, the major histone-like protein of E. coli, modulates the binding of IHF to oriC., EMBO J. 11(12):4489-96

 [42] 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):781-92

 [43] 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):1069-79

 [44] 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):443-8

 [45] Kamashev D., Balandina A., Rouviere-Yaniv J., 1999, The binding motif recognized by HU on both nicked and cruciform DNA., EMBO J. 18(19):5434-44

 [46] 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):442-6

 [47] 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):353-70

 [48] 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):5568-77

 [49] 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):278-89

 [50] Macvanin M., Adhya S., 2012, Architectural organization in E. coli nucleoid., Biochim Biophys Acta. 1819(7):830-5