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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 [17, 18] and regulation [1, 7, 8, 15]. HU is a heterodimer formed by an α-subunit and a β-subunit, which are encoded by the hupA and hupB genes, respectively [5, 19] and are differentially stimulated during cold shock [] 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 [5] HU forms high-affinity complexes with DNA containing sharp bends, kinks, branched and bulged structures, or single-strand breaks and loops [14] Three dimeric forms of HU exist in Escherichia coli: two homodimers, EcHUα2 and EcHUβ2, and a heterodimer, HUαβ [20] All these forms are in thermal equilibrium between two dimeric conformations (N2↔I2) that vary in their secondary structure content [] 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) []. 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 [] A 3D model has been proposed for the major I2 conformation of EcHUβ2 [] The crystal structure of the DNA-HUαβ complex has been resolved [21] In the presence of poly(P), HupA is efficiently degraded by Lon [] The presence of HU depends on the phase of growth [] and it is distributed uniformly in the nucleoid [18] Currently, no inducer for this regulator has been reported in the literature.
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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   [AIFS], [APPH], [GEA] [1], [2], [3], [4], [5], [6], [7], [8], [9], [10]
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)
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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
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

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 galEp1 Sigma70, Sigma38 6.5 -20.5 galE, galT, galK, galM
792059 792092 [BPP], [GEA] [1], [9], [11], [12], [13], [14], [15]
  HU repressor galEp2 Sigma70 6.5 -25.5 galE, galT, galK, galM
792064 792097 [BPP], [GEA] [1], [9], [11], [13], [14], [15]
  HU activator micFp Sigma70 nd -2313084.0 micF nd nd [GEA] [8]
  HU repressor mtrp2 Sigma70 nd 3305817.0 mtr nd nd [GEA] [16]
  HU repressor seqAp nd nd -712987.0 seqA, pgm nd nd [GEA] [7]
  HU repressor tyrPp1 Sigma70 nd -1989681.0 tyrP nd nd [GEA] [16]

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


 [AIFS] Automated inference of function from sequence

 [APPH] Assay of protein purified to homogeneity

 [GEA] Gene expression analysis

 [BPP] Binding of purified proteins


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

 [2] Broyles SS., Pettijohn DE., 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(1):47-60

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

 [4] Delihas N., Forst S., 2001, MicF: an antisense RNA gene involved in response of Escherichia coli to global stress factors., J Mol Biol 313(1):1-12

 [5] 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

 [6] Laine B., Sautiere P., Biserte G., Cohen-Solal M., Gros F., Rouviere-Yaniv J., 1978, The amino- and carboxy-terminal amino acid sequences of protein HU from Escherichia coli., FEBS Lett 89(1):116-20

 [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] 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] 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

 [10] Rouviere-Yaniv J., Kjeldgaard NO., 1979, Native Escherichia coli HU protein is a heterotypic dimer., FEBS Lett 106(2):297-300

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

 [12] 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

 [13] 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

 [14] 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

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

 [16] 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

 [17] 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

 [18] 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

 [19] 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

 [20] 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

 [21] 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

 [22] 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

 [23] 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