Summary: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains and consist of several OPERONS.

Top Publications

  1. Pratt J, Ismail A, Camilli A. PhoB regulates both environmental and virulence gene expression in Vibrio cholerae. Mol Microbiol. 2010;77:1595-605 pubmed publisher
    ..Here, we show that the P(i) (Pho) regulon, which is controlled by the P(i)-specific transporter (Pst) and two-component system PhoBR, is required for V...
  2. Balasubramanian D, Kumari H, Jaric M, Fernandez M, Turner K, Dove S, et al. Deep sequencing analyses expands the Pseudomonas aeruginosa AmpR regulon to include small RNA-mediated regulation of iron acquisition, heat shock and oxidative stress response. Nucleic Acids Res. 2014;42:979-98 pubmed publisher
    ..Using RNA-Seq and complementary assays, this study further expands the AmpR regulon to include diverse processes such as oxidative stress, heat shock and iron uptake...
  3. da Silva Neto J, Lourenço R, Marques M. Global transcriptional response of Caulobacter crescentus to iron availability. BMC Genomics. 2013;14:549 pubmed publisher
    ..However, the impact of the iron availability on the C. crescentus transcriptome and an overall perspective of the regulatory networks involved remain unknown...
  4. Leyn S, Kazanov M, Sernova N, Ermakova E, Novichkov P, Rodionov D. Genomic reconstruction of the transcriptional regulatory network in Bacillus subtilis. J Bacteriol. 2013;195:2463-73 pubmed publisher
    ..projected them to other Bacillales genomes, resulting in refinement of TFBS motifs and identification of novel regulon members...
  5. Caswell C, Elhassanny A, Planchin E, Roux C, Weeks Gorospe J, Ficht T, et al. Diverse genetic regulon of the virulence-associated transcriptional regulator MucR in Brucella abortus 2308. Infect Immun. 2013;81:1040-51 pubmed publisher
    ..Overall, these studies have uncovered the diverse genetic regulon of MucR in Brucella, and in doing so this work has begun to define the MucR-controlled genetic circuitry whose ..
  6. Cheng C, Wakefield M, Yang J, Tauschek M, Robins Browne R. Genome-wide analysis of the Pho regulon in a pstCA mutant of Citrobacter rodentium. PLoS ONE. 2012;7:e50682 pubmed publisher
    The phosphate-specific transport operon, pstSCAB-phoU, of Gram-negative bacteria is an essential part of the Pho regulon. Its key roles are to encode a high-affinity inorganic phosphate transport system and to prevent activation of PhoB ..
  7. Sobrero P, Schlüter J, Lanner U, Schlosser A, Becker A, Valverde C. Quantitative proteomic analysis of the Hfq-regulon in Sinorhizobium meliloti 2011. PLoS ONE. 2012;7:e48494 pubmed publisher
    ..These results represent the first quantitative proteomic analysis in S. meliloti. The comparative analysis of the hfq mutant proteome allowed identification of novel strongly Hfq-regulated genes in S. meliloti...
  8. Lavy T, Kumar P, He H, Joshua Tor L. The Gal3p transducer of the GAL regulon interacts with the Gal80p repressor in its ligand-induced closed conformation. Genes Dev. 2012;26:294-303 pubmed publisher
    A wealth of genetic information and some biochemical analysis have made the GAL regulon of the yeast Saccharomyces cerevisiae a classic model system for studying transcriptional activation in eukaryotes...
  9. Saujet L, Monot M, Dupuy B, Soutourina O, Martin Verstraete I. The key sigma factor of transition phase, SigH, controls sporulation, metabolism, and virulence factor expression in Clostridium difficile. J Bacteriol. 2011;193:3186-96 pubmed publisher
    ..Among the 286 genes positively regulated by SigH, about 40 transcriptional units presenting a SigH consensus in their promoter regions are good candidates for direct SigH targets. ..

More Information


  1. Bitoun J, Nguyen A, Fan Y, Burne R, Wen Z. Transcriptional repressor Rex is involved in regulation of oxidative stress response and biofilm formation by Streptococcus mutans. FEMS Microbiol Lett. 2011;320:110-7 pubmed publisher
    ..These results reveal that Rex plays an important role in oxidative stress responses and biofilm formation by S. mutans. ..
  2. Sastalla I, Maltese L, Pomerantseva O, Pomerantsev A, Keane Myers A, Leppla S. Activation of the latent PlcR regulon in Bacillus anthracis. Microbiology. 2010;156:2982-93 pubmed publisher
    ..cereus. We found that activation of the PlcR regulon in B...
  3. Doroshenko V, Tsyrenzhapova I, Krylov A, Kiseleva E, Ermishev V, Kazakova S, et al. Pho regulon promoter-mediated transcription of the key pathway gene aroGFbr improves the performance of an L-phenylalanine-producing Escherichia coli strain. Appl Microbiol Biotechnol. 2010;88:1287-95 pubmed publisher
    ..The choice of promoter was based on the detected activation of the Pho regulon that occurs in response to the depletion of soluble inorganic orthophosphate (P(i)) in the medium, provided that ..
  4. Castells Roca L, Muhlenhoff U, Lill R, Herrero E, Belli G. The oxidative stress response in yeast cells involves changes in the stability of Aft1 regulon mRNAs. Mol Microbiol. 2011;81:232-48 pubmed publisher
    ..Aft1 is transitorily internalized into the nucleus, followed by transcription activation of components of its regulon. In these conditions, the mRNA levels of the genes of the non-reductive pathway become increased, while those of ..
  5. Ding C, Yin J, Tovar E, Fitzpatrick D, Higgins D, Thiele D. The copper regulon of the human fungal pathogen Cryptococcus neoformans H99. Mol Microbiol. 2011;81:1560-76 pubmed publisher
    ..These studies set the stage for the evaluation of the specific Cuf1 target genes required for virulence in C. neoformans. ..
  6. Sun J, Glass N. Identification of the CRE-1 cellulolytic regulon in Neurospora crassa. PLoS ONE. 2011;6:e25654 pubmed publisher
    ..We determined the CRE-1 regulon by investigating the secretome and transcriptome of a ?cre-1 strain as compared to wild type when grown on Avicel ..
  7. Wada T, Tanabe Y, Kutsukake K. FliZ acts as a repressor of the ydiV gene, which encodes an anti-FlhD4C2 factor of the flagellar regulon in Salmonella enterica serovar typhimurium. J Bacteriol. 2011;193:5191-8 pubmed publisher
    ..These results indicate that FliZ is a repressor of the nlpC-ydiV operon and activates the class 2 operons by repressing ydiV expression. Therefore, the fliZ and ydiV genes form a regulatory loop...
  8. Leyn S, Gao F, Yang C, Rodionov D. N-acetylgalactosamine utilization pathway and regulon in proteobacteria: genomic reconstruction and experimental characterization in Shewanella. J Biol Chem. 2012;287:28047-56 pubmed publisher
    ..This study provides comprehensive insights into the common and distinctive features of the GalNAc/GalN catabolism and its regulation in diverse Proteobacteria...
  9. Suvorova I, Tutukina M, Ravcheev D, Rodionov D, Ozoline O, Gelfand M. Comparative genomic analysis of the hexuronate metabolism genes and their regulation in gammaproteobacteria. J Bacteriol. 2011;193:3956-63 pubmed publisher
    ..We provide experimental evidence that two predicted members of the UxuR regulon, yjjM and yjjN, are the subject of complex regulation by this transcription factor in E. coli.
  10. Motohashi R, Rödiger A, Agne B, Baerenfaller K, Baginsky S. Common and specific protein accumulation patterns in different albino/pale-green mutants reveals regulon organization at the proteome level. Plant Physiol. 2012;160:2189-201 pubmed publisher
    ..Our analysis provides initial guidance for the distinction between general and specific adaptations of the proteome in photosynthesis-impaired plants. ..
  11. Britos L, Abeliuk E, Taverner T, Lipton M, McAdams H, Shapiro L. Regulatory response to carbon starvation in Caulobacter crescentus. PLoS ONE. 2011;6:e18179 pubmed publisher
    ..Also, cell pole morphogenesis and initiation of chromosome replication normally occurring at the swarmer-to-stalked cell transition are uncoupled in carbon-starved cells. ..
  12. Raghavan R, Sage A, Ochman H. Genome-wide identification of transcription start sites yields a novel thermosensing RNA and new cyclic AMP receptor protein-regulated genes in Escherichia coli. J Bacteriol. 2011;193:2871-4 pubmed publisher
  13. Faye M, Graber T, Liu P, Thakor N, Baird S, Durie D, et al. Nucleotide composition of cellular internal ribosome entry sites defines dependence on NF45 and predicts a posttranscriptional mitotic regulon. Mol Cell Biol. 2013;33:307-18 pubmed publisher
    ..This study uncovers a novel role for NF45 in regulating ploidy and highlights the importance of IRES-mediated translation in cellular homeostasis. ..
  14. Rice J, Vanderpool C. The small RNA SgrS controls sugar-phosphate accumulation by regulating multiple PTS genes. Nucleic Acids Res. 2011;39:3806-19 pubmed publisher
    ..A ptsG manXYZ double mutant is resistant to the stress, indicating that PTS transporters encoded by both SgrS targets are involved in taking up substrates that cause stress. ..
  15. Grudniak A, Kurek A, Szarlak J, Wolska K. Oleanolic and ursolic acids influence affect the expression of the cysteine regulon and the stress response in Escherichia coli. Curr Microbiol. 2011;62:1331-6 pubmed publisher
    ..coli cysteine regulon, cysPTWA, cysJIH, and cysB, by using transcriptional fusions with the lacZ reporter gene...
  16. Shimada T, Yamamoto K, Ishihama A. Novel members of the Cra regulon involved in carbon metabolism in Escherichia coli. J Bacteriol. 2011;193:649-59 pubmed publisher
    ..Taken together, we propose that Cra plays a key role in balancing the levels of the enzymes for carbon metabolism. ..
  17. Gerken H, Misra R. MzrA-EnvZ interactions in the periplasm influence the EnvZ/OmpR two-component regulon. J Bacteriol. 2010;192:6271-8 pubmed publisher
    ..Together, the data suggest that the binding of MzrA to EnvZ influences the ability of EnvZ to receive and/or respond to environmental signals in the periplasm and modulate its biochemical output to OmpR...
  18. Damron F, Owings J, Okkotsu Y, Varga J, Schurr J, Goldberg J, et al. Analysis of the Pseudomonas aeruginosa regulon controlled by the sensor kinase KinB and sigma factor RpoN. J Bacteriol. 2012;194:1317-30 pubmed publisher
    ..To determine the RpoN-dependent KinB regulon, microarray and proteomic analyses were performed on a mucoid kinB mutant and an isogenic nonmucoid kinB rpoN ..
  19. Wang R, Mast Y, Wang J, Zhang W, Zhao G, Wohlleben W, et al. Identification of two-component system AfsQ1/Q2 regulon and its cross-regulation with GlnR in Streptomyces coelicolor. Mol Microbiol. 2013;87:30-48 pubmed publisher
    ..underlying the function of AfsQ1/Q2 on antibiotic production and also the identification of the AfsQ1/Q2 regulon. The results showed that AfsQ1/Q2 stimulated antibiotic ACT, RED and CDA production directly through the pathway-..
  20. Kumar A, Majid M, Kunisch R, Rani P, Qureshi I, Lewin A, et al. Mycobacterium tuberculosis DosR regulon gene Rv0079 encodes a putative, 'dormancy associated translation inhibitor (DATIN)'. PLoS ONE. 2012;7:e38709 pubmed publisher
    ..The regulation of M. tuberculosis metabolism during latent infection is not clearly known. The dormancy survival regulon (DosR regulon) is chiefly responsible for encoding dormancy related functions of M. tuberculosis...
  21. Chekabab S, Daigle F, Charette S, Dozois C, Harel J. Survival of enterohemorrhagic Escherichia coli in the presence of Acanthamoeba castellanii and its dependence on Pho regulon. Microbiologyopen. 2012;1:427-37 pubmed publisher
    ..Using several mutants, we observed that the Pho regulon is required for EHEC growth when cocultured with amoebae...
  22. Richards G, Vanderpool C. Induction of the Pho regulon suppresses the growth defect of an Escherichia coli sgrS mutant, connecting phosphate metabolism to the glucose-phosphate stress response. J Bacteriol. 2012;194:2520-30 pubmed publisher
    ..Microarray analysis suggested that expression of phosphate (Pho) regulon genes is increased in the sgrS pitA mutant compared to the sgrS parent...
  23. Ryo S, Ishii J, Iguchi Y, Fukuda N, Kondo A. Transplantation of the GAL regulon into G-protein signaling circuitry in yeast. Anal Biochem. 2012;424:27-31 pubmed publisher
    ..The GAL regulon represents a strictly regulated transcriptional mechanism that we have transplanted into yeast to create a highly ..
  24. Gogol E, Rhodius V, Papenfort K, Vogel J, Gross C. Small RNAs endow a transcriptional activator with essential repressor functions for single-tier control of a global stress regulon. Proc Natl Acad Sci U S A. 2011;108:12875-80 pubmed publisher
  25. Sullivan J, Brown S, Ronson C. The NifA-RpoN regulon of Mesorhizobium loti strain R7A and its symbiotic activation by a novel LacI/GalR-family regulator. PLoS ONE. 2013;8:e53762 pubmed publisher
    ..loti and to characterise the NifA-RpoN regulon. The nifA2 and rpoN2 genes were essential for nitrogen fixation whereas nifA1 and rpoN1 were dispensable...
  26. Apostu R, Mackey M. Mathematical model of GAL regulon dynamics in Saccharomyces cerevisiae. J Theor Biol. 2012;293:219-35 pubmed publisher
    ..2010). Furthermore, the computational modeling provides an explanation for the contradictory results obtained by independent laboratories when tackling experimentally the issue of binary versus graded response to galactose induction. ..
  27. Wada T, Morizane T, Abo T, Tominaga A, Inoue Tanaka K, Kutsukake K. EAL domain protein YdiV acts as an anti-FlhD4C2 factor responsible for nutritional control of the flagellar regulon in Salmonella enterica Serovar Typhimurium. J Bacteriol. 2011;193:1600-11 pubmed publisher
    ..Taking these data together, we conclude that YdiV is a novel anti-FlhD(4)C(2) factor responsible for nutritional control of the flagellar regulon.
  28. Chaturongakul S, Raengpradub S, Palmer M, Bergholz T, Orsi R, Hu Y, et al. Transcriptomic and phenotypic analyses identify coregulated, overlapping regulons among PrfA, CtsR, HrcA, and the alternative sigma factors sigmaB, sigmaC, sigmaH, and sigmaL in Listeria monocytogenes. Appl Environ Microbiol. 2011;77:187-200 pubmed publisher
  29. Bertrand N, Houle S, LeBihan G, Poirier É, Dozois C, Harel J. Increased Pho regulon activation correlates with decreased virulence of an avian pathogenic Escherichia coli O78 strain. Infect Immun. 2010;78:5324-31 pubmed publisher
    ..The Pho regulon is jointly controlled by the two-component regulatory system PhoBR and by the phosphate-specific transport (Pst) ..
  30. Labandeira Rey M, Brautigam C, Hansen E. Characterization of the CpxRA regulon in Haemophilus ducreyi. Infect Immun. 2010;78:4779-91 pubmed publisher
    ..A cpxA deletion mutant and a CpxR-overexpressing strain were used to explore the extent of the CpxRA regulon. DNA microarray and real-time reverse transcriptase (RT) PCR analyses indicated several potential regulatory ..
  31. Ramachandran R, Stevens A. Proteomic analysis of the quorum-sensing regulon in Pantoea stewartii and identification of direct targets of EsaR. Appl Environ Microbiol. 2013;79:6244-52 pubmed publisher
    ..Proteomic analysis identified a QS regulon of more than 30 proteins...
  32. Troxell B, Fink R, Porwollik S, McClelland M, Hassan H. The Fur regulon in anaerobically grown Salmonella enterica sv. Typhimurium: identification of new Fur targets. BMC Microbiol. 2011;11:236 pubmed publisher
    ..e., in ambient oxygen concentration. To reveal potentially novel aspects of the Fur regulon in Salmonella enterica serovar Typhimurium under oxygen conditions similar to that encountered in the host, we ..
  33. Pátek M, Nesvera J. Sigma factors and promoters in Corynebacterium glutamicum. J Biotechnol. 2011;154:101-13 pubmed publisher
    ..Each sigma factor is responsible for recognizing promoters of genes belonging to a regulon (sigmulon) involved in specific functions of the cell. Most promoters of C...
  34. den Hengst C, Tran N, Bibb M, Chandra G, Leskiw B, Buttner M. Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Mol Microbiol. 2010;78:361-79 pubmed
    ..Here we identify the BldD regulon by means of chromatin immunoprecipitation-microarray analysis (ChIP-chip)...
  35. Chubiz L, Glekas G, Rao C. Transcriptional cross talk within the mar-sox-rob regulon in Escherichia coli is limited to the rob and marRAB operons. J Bacteriol. 2012;194:4867-75 pubmed publisher
    ..In this work, we systematically investigated the extent of transcriptional cross talk in the mar-sox-rob regulon. While the three transcription factors were found to have the potential to regulate each other's expression when ..
  36. Butcher B, Bronstein P, Myers C, Stodghill P, Bolton J, Markel E, et al. Characterization of the Fur regulon in Pseudomonas syringae pv. tomato DC3000. J Bacteriol. 2011;193:4598-611 pubmed publisher
    ..regulator of iron homeostasis is Fur (ferric uptake regulator), and here we present the first study of the Fur regulon in DC3000...
  37. Png K, Halberg N, Yoshida M, Tavazoie S. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2011;481:190-4 pubmed publisher
    ..Our work further reveals endothelial recruitment and endothelial interactions in the tumour microenvironment to be critical features of metastatic breast cancer. ..
  38. Ahn S, Qu M, Roberts E, Burne R, Rice K. Identification of the Streptococcus mutans LytST two-component regulon reveals its contribution to oxidative stress tolerance. BMC Microbiol. 2012;12:187 pubmed publisher
    ..In this study, we sought to determine if LytST was involved in regulating lrgAB expression in response to glucose and oxygenation in S. mutans...
  39. Voigt B, Schroeter R, Jürgen B, Albrecht D, Evers S, Bongaerts J, et al. The response of Bacillus licheniformis to heat and ethanol stress and the role of the SigB regulon. Proteomics. 2013;13:2140-61 pubmed publisher
    ..licheniformis, such as the HrcA, SigB, CtsR, and CssRS regulon. Upregulation of the SigY regulon and of genes controlled by other extracytoplasmic function (ECF) sigma factors ..
  40. Rodionov D, Novichkov P, Stavrovskaya E, Rodionova I, Li X, Kazanov M, et al. Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus. BMC Genomics. 2011;12 Suppl 1:S3 pubmed publisher
    ..Multiple variations in regulatory strategies between the Shewanella spp. and E. coli include regulon contraction and expansion (as in the case of PdhR, HexR, FadR), numerous cases of recruiting non-orthologous ..
  41. De Majumdar S, Veleba M, Finn S, Fanning S, Schneiders T. Elucidating the regulon of multidrug resistance regulator RarA in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2013;57:1603-9 pubmed publisher
    ..pneumoniae. Given its phenotypic role in MDR, microarray analyses were performed to determine the RarA regulon. Transcriptome analysis was undertaken using strains Ecl8?rarA/pACrarA-2 (rarA-expressing construct) and Ecl8?..
  42. Gu M, Imlay J. The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide. Mol Microbiol. 2011;79:1136-50 pubmed publisher
    ..In aerobic cells these drugs generate superoxide, and because superoxide dismutase (SOD) is a member of the SoxRS regulon, superoxide was initially thought to be the activator of SoxR...
  43. Chugani S, Kim B, Phattarasukol S, Brittnacher M, Choi S, Harwood C, et al. Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon. Proc Natl Acad Sci U S A. 2012;109:E2823-31 pubmed publisher
    ..This study also provides a framework for understanding the molecular mechanisms by which quorum-sensing systems operate, the evolutionary pressures by which they are maintained, and their importance in disparate ecological contexts. ..
  44. Falord M, Mäder U, Hiron A, Debarbouille M, Msadek T. Investigation of the Staphylococcus aureus GraSR regulon reveals novel links to virulence, stress response and cell wall signal transduction pathways. PLoS ONE. 2011;6:e21323 pubmed publisher
    ..stress reponse and cell wall metabolism signal transduction pathways, sharing an extensive overlap with the WalKR regulon. This is the first report showing a role for the GraSR TCS in high temperature and oxidative stress survival and ..
  45. Jones A, Fulcher N, Balzer G, Urbanowski M, Pritchett C, Schurr M, et al. Activation of the Pseudomonas aeruginosa AlgU regulon through mucA mutation inhibits cyclic AMP/Vfr signaling. J Bacteriol. 2010;192:5709-17 pubmed publisher
    ..These results suggest that mucoid conversion and inhibition of invasive virulence determinants may both confer a selective advantage to mucA mutant strains of P. aeruginosa in the CF lung. ..
  46. Novichkov P, Rodionov D, Stavrovskaya E, Novichkova E, Kazakov A, Gelfand M, et al. RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach. Nucleic Acids Res. 2010;38:W299-307 pubmed publisher
    ..Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several ..
  47. Borg M, Brownfield L, Khatab H, Sidorova A, Lingaya M, Twell D. The R2R3 MYB transcription factor DUO1 activates a male germline-specific regulon essential for sperm cell differentiation in Arabidopsis. Plant Cell. 2011;23:534-49 pubmed publisher
    ..This work advances knowledge of the DUO1 regulon that encompasses genes with a range of cellular functions, including transcription, protein fate, signaling, and ..
  48. Cho B, Federowicz S, Embree M, Park Y, Kim D, Palsson B. The PurR regulon in Escherichia coli K-12 MG1655. Nucleic Acids Res. 2011;39:6456-64 pubmed publisher
    ..Compared to the functional diversity of the regulon of the other general transcription factors in E. coli, the functions and size of the PurR regulon are limited.
  49. Karlinsey J, Bang I, Becker L, Frawley E, Porwollik S, Robbins H, et al. The NsrR regulon in nitrosative stress resistance of Salmonella enterica serovar Typhimurium. Mol Microbiol. 2012;85:1179-93 pubmed publisher
    ..Additionally, we have defined the NsrR regulon in Salmonella enterica sv. Typhimurium 14028s using transcriptional microarray, qRT-PCR and in silico methods...
  50. Dong T, Mekalanos J. Characterization of the RpoN regulon reveals differential regulation of T6SS and new flagellar operons in Vibrio cholerae O37 strain V52. Nucleic Acids Res. 2012;40:7766-75 pubmed publisher
    ..The RpoN regulon has yet to be clearly defined in T6SS-active V...
  51. Gerasimova A, Kazakov A, Arkin A, Dubchak I, Gelfand M. Comparative genomics of the dormancy regulons in mycobacteria. J Bacteriol. 2011;193:3446-52 pubmed publisher
    ..This process is regulated by the DosR transcription factor. In Mycobacterium tuberculosis, the dormancy regulon is well characterized and contains the dosR gene itself and dosS and dosT genes encoding DosR kinases, ..
  52. Balbontin R, Fiorini F, Figueroa Bossi N, Casadesus J, Bossi L. Recognition of heptameric seed sequence underlies multi-target regulation by RybB small RNA in Salmonella enterica. Mol Microbiol. 2010;78:380-94 pubmed
    ..specificity identified chiP (ybfM), a gene encoding an inducible chitoporin, as an additional member of the RybB regulon. Altogether, our results indicate that an heptameric 'seed' sequence is sufficient to confer susceptibility to ..
  53. Cheng X, de Bruijn I, van der Voort M, Loper J, Raaijmakers J. The Gac regulon of Pseudomonas fluorescens SBW25. Environ Microbiol Rep. 2013;5:608-19 pubmed publisher
    ..Similar to the Gac regulon of other Pseudomonas species, genes involved in motility, biofilm formation, siderophore biosynthesis and ..