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Gene Review

hetR  -  heterocyst differentiation control protein

Nostoc sp. PCC 7120

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Disease relevance of hetR


High impact information on hetR

  • Overexpression of a 54-base-pair gene, patS, blocked heterocyst differentiation in Anabaena sp. strain PCC 7120 [4].
  • Interruption of the hetR gene in wild-type cells results in a mutant phenotype identical to that of 216 [5].
  • Both 216 and wild-type cells containing wild-type hetR on a plasmid display increased frequency of heterocysts, even on media containing fixed nitrogen [5].
  • The mutation in 216 is located at nucleotide 535 in the hetR gene, converting a serine at position 179 in the wild-type protein to an asparagine in the mutant [5].
  • We show here that the sequence of this fragment contains a single open reading frame (hetR), encoding a 299-amino-acid protein [5].

Chemical compound and disease context of hetR


Biological context of hetR


Associations of hetR with chemical compounds

  • We demonstrate here that CcbP is degraded by HetR, a serine-type protease that controls heterocyst differentiation [6].
  • The increase of 2-oxoglutarate within cells can trigger heterocyst differentiation in a subpopulation of filaments even in the presence of nitrate [11].
  • These results suggest that Ca(2+) ions play very important roles in hetR induction and heterocyst differentiation [12].
  • Heterocyst development (which is necessary for the aerobic fixation of dinitrogen) and induction of hetR (a regulatory gene that is required for heterocyst development) were also impaired in the ntcA mutant [13].
  • Use of luxAB, encoding luciferase, as a reporter, and use of luxC, luxD and luxE to generate aldehyde (a substrate for the luciferase reaction), permitted visualization of the expression of hetR at the level of single cells; hetR was expressed in akinetes [2].

Regulatory relationships of hetR

  • The patA mutation suppresses the multiheterocyst phenotype produced by extra copies of the wild-type hetR gene described previously, suggesting that PatA and HetR are components of the same environment-sensing regulatory circuit in Anabaena [14].
  • A patS-gfp reporter strain revealed clusters of patS-expressing cells during the early stage of heterocyst differentiation [15].

Other interactions of hetR

  • We present evidence that shows that the up-regulation of patS and hetR depends on DNA binding by HetR dimer [7].
  • Overexpression of ntcA in a hetR background promoted expression of devBCA in response to ammonium withdrawal and excision of the 11-kb element even in the presence of combined nitrogen [8].
  • The transcription regulator NtcA is required for the initiation of heterocyst formation. hetL overexpression allowed the initiation of heterocyst development in an ntcA-null mutant, but differentiation was incomplete. hetR and hetC mutations that block heterocyst development are epistatic to hetL overexpression [16].
  • Suppression of heterocyst formation by HetN appears to occur both upstream and downstream of the positive regulator HetR: overexpression of hetN in undifferentiated filaments prevents the wild-type pattern of hetR expression as well as the multiheterocyst phenotype normally observed when hetR is expressed from an inducible promoter [17].
  • In contrast to the hetR mutant, a hetP mutant of N. ellipsosporum could form akinetes, but heterocyst formation was blocked [2].

Analytical, diagnostic and therapeutic context of hetR


  1. Identification of the active site of HetR protease and its requirement for heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120. Dong, Y., Huang, X., Wu, X.Y., Zhao, J. J. Bacteriol. (2000) [Pubmed]
  2. Two mutations that block heterocyst differentiation have different effects on akinete differentiation in Nostoc ellipsosporum. Leganés, F., Fernández-Piñas, F., Wolk, C.P. Mol. Microbiol. (1994) [Pubmed]
  3. Characterization of HetR protein turnover in Anabaena sp. PCC 7120. Zhou, R., Cao, Z., Zhao, J. Arch. Microbiol. (1998) [Pubmed]
  4. Heterocyst pattern formation controlled by a diffusible peptide. Yoon, H.S., Golden, J.W. Science (1998) [Pubmed]
  5. Characterization of a gene controlling heterocyst differentiation in the cyanobacterium Anabaena 7120. Buikema, W.J., Haselkorn, R. Genes Dev. (1991) [Pubmed]
  6. Regulation of intracellular free calcium concentration during heterocyst differentiation by HetR and NtcA in Anabaena sp. PCC 7120. Shi, Y., Zhao, W., Zhang, W., Ye, Z., Zhao, J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. HetR homodimer is a DNA-binding protein required for heterocyst differentiation, and the DNA-binding activity is inhibited by PatS. Huang, X., Dong, Y., Zhao, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. HetR-dependent and -independent expression of heterocyst-related genes in an Anabaena strain overproducing the NtcA transcription factor. Olmedo-Verd, E., Flores, E., Herrero, A., Muro-Pastor, A.M. J. Bacteriol. (2005) [Pubmed]
  9. NrrA Directly Regulates Expression of hetR during Heterocyst Differentiation in the Cyanobacterium Anabaena sp. Strain PCC 7120. Ehira, S., Ohmori, M. J. Bacteriol. (2006) [Pubmed]
  10. Mutual dependence of the expression of the cell differentiation regulatory protein HetR and the global nitrogen regulator NtcA during heterocyst development. Muro-Pastor, A.M., Valladares, A., Flores, E., Herrero, A. Mol. Microbiol. (2002) [Pubmed]
  11. An increase in the level of 2-oxoglutarate promotes heterocyst development in the cyanobacterium Anabaena sp. strain PCC 7120. Li, J.H., Laurent, S., Konde, V., Bédu, S., Zhang, C.C. Microbiology (Reading, Engl.) (2003) [Pubmed]
  12. CcbP, a calcium-binding protein from Anabaena sp. PCC 7120, provides evidence that calcium ions regulate heterocyst differentiation. Zhao, Y., Shi, Y., Zhao, W., Huang, X., Wang, D., Brown, N., Brand, J., Zhao, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. Requirement of the regulatory protein NtcA for the expression of nitrogen assimilation and heterocyst development genes in the cyanobacterium Anabaena sp. PCC 7120. Frías, J.E., Flores, E., Herrero, A. Mol. Microbiol. (1994) [Pubmed]
  14. The patA gene product, which contains a region similar to CheY of Escherichia coli, controls heterocyst pattern formation in the cyanobacterium Anabaena 7120. Liang, J., Scappino, L., Haselkorn, R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  15. PatS and products of nitrogen fixation control heterocyst pattern. Yoon, H.S., Golden, J.W. J. Bacteriol. (2001) [Pubmed]
  16. hetL overexpression stimulates heterocyst formation in Anabaena sp. strain PCC 7120. Liu, D., Golden, J.W. J. Bacteriol. (2002) [Pubmed]
  17. The role of HetN in maintenance of the heterocyst pattern in Anabaena sp. PCC 7120. Callahan, S.M., Buikema, W.J. Mol. Microbiol. (2001) [Pubmed]
  18. Host specificity in the Richelia-diatom symbiosis revealed by hetR gene sequence analysis. Janson, S., Wouters, J., Bergman, B., Carpenter, E.J. Environ. Microbiol. (1999) [Pubmed]
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