Catabolite repression and activation in Bacillus subtilis: dependency on CcpA, HPr, and HprK.
Previous studies have suggested that the transcription factor CcpA, as well as the coeffectors HPr and Crh, both phosphorylated by the HprK kinase/phosphorylase, are primary mediators of catabolite repression and catabolite activation in Bacillus subtilis. We here report whole transcriptome analyses that characterize glucose-dependent gene expression in wild-type cells and in isogenic mutants lacking CcpA, HprK, or the HprK phosphorylatable serine in HPr. Binding site identification revealed which genes are likely to be primarily or secondarily regulated by CcpA. Most genes subject to CcpA-dependent regulation are regulated fully by HprK and partially by serine-phosphorylated HPr [HPr(Ser-P)]. A positive linear correlation was noted between the dependencies of catabolite-repressible gene expression on CcpA and HprK, but no such relationship was observed for catabolite-activated genes, suggesting that large numbers of the latter genes are not regulated by the CcpA-HPr(Ser-P) complex. Many genes that mediate nitrogen or phosphorus metabolism as well as those that function in stress responses proved to be subject to CcpA-dependent glucose control. While nitrogen-metabolic genes may be subject to either glucose repression or activation, depending on the gene, almost all glucose-responsive phosphorus-metabolic genes exhibit activation while almost all glucose-responsive stress genes show repression. These responses are discussed from physiological standpoints. These studies expand our appreciation of CcpA-mediated catabolite control and provide insight into potential interregulon control mechanisms in gram-positive bacteria.
Lorca
Graciela L
GL
Division of Biological Sciences, University of California at San Diego, La Jolla, 92093-0116, USA.
Chung
Yong Joon
YJ
Barabote
Ravi D
RD
Weyler
Walter
W
Schilling
Christophe H
CH
Saier
Milton H
MH
D000222:Adaptation, Physiological; D001412:Bacillus subtilis / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010758:Phosphorus / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012329:RNA, Bacterial / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012097:Repressor Proteins; C442131:ScoC protein, Bacillus subtilis; D014157:Transcription Factors; C069286:catabolite control proteins, bacteria; D010758:Phosphorus; C110847:HPr kinase; D017346:Protein Serine-Threonine Kinases; D005947:Glucose; D009584:Nitrogen