RegulonDB

lacZYA operon and associated TUs in Escherichia coli K-12 genome

Operon
Name:	lacZYA
This page displays every known transcription unit of this operon and their known regulation.

Transcription unit

Name:	lacZYA
Synonym(s):	OP00045, lacAYZ
Gene(s):	lacA, lacY, lacZ Genome Browser M3D Gene expression COLOMBOS
Note(s):	The lac operon is controlled by four promoters, P1, which is the principal promoter, P2, and P3 and P4, the weaker promoters Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991. Transcription of this operon is both negatively and positively regulated. Negative regulation occurs when the lac repressor (LacI) binds to the operator, preventing transcription by RNA polymerase Schmitz A.,1981. Hudson JM,1990. Positive regulation is mediated by the cAMP receptor protein, CRP (also referred to as the catabolite activator protein, CAP) Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991. Liu M,2004 In the presence of glucose, lac operon expression is not needed and a control mechanism known as catabolite repression occurs. This refers to the ability of glucose to inhibit expression of the operon. As cellular cAMP levels drop in response to glucose uptake, CRP is not activated and operon expression is inhibited. Under this mechanism, lac genes are only expressed if lactose is present and glucose is absent. In the absence of glucose, the levels of cAMP increase and this metabolite binds to CRP. CRP becomes active and it binds to DNA near the lac promoter, facilitating transcription Schmitz A.,1981. Hudson JM,1990. Synthesis of the lac operon proteins is induced when E. coli is grown on lactose in the absence of glucose. CRP is the principal activator of the lac operon. CRP interacts with RNA polymerase and stimulates transcription of lacZp1 by increasing the binding of the RNA polymerase and the open complex stabilization Liu M,2003. Savery N,1996. Noel RJ,1998. In the same way, CRP completely overlaps lacZp2 and lacZp3, avoiding RNA polymerase binding and preventing transcription of these promoters Hudson JM,1990. Eschenlauer AC, Reznikoff WS,1991. Xiong XF,1991. On the other hand, in the absence of allolactose, the LacI repressor represses the lac operon Hudson JM,1990. Lewis M.,2005. In this repression system, LacI binds to two operators centered at positions 10 bp (O1) and -82 bp (O3), and formation of the repressor loop is critical Fried MG, Hudson JM,1996. Perros M, Steitz TA,1996. Balaeff A, Mahadevan L, Schulten K,2004. Hudson JM,1990. Expression of p1 is also stimulated when LacI binds to O1 Hudson JM,1990. Induction occurs when the physiological inducer, allolactose, binds to the lac repressor, preventing it from binding to the operator Hudson JM,1990. Lewis M.,2005. Nonphysiological analogs, such as thiogalactosides, can function as inducers too. Activation of the lac operon can also be partially increased by CRP when it overlaps the O1 site, acting as an antirepressor Straney SB, Crothers DM,1987. Hudson JM,1990. In single-cell experiments, total induction of the lac operon produces a constant distribution in the production of mRNA molecules in all growth phases, except in the exponential phase, where two mRNA populations are present Sala A, Shoaib M, Anufrieva O, Mutharasu G, Yli-Harja O, Kandhavelu M,2015. Considering the activation site of the lac operon like the upstream activation region of the promoter sequence (URS) and the operator region like downstream derepression region of the promoter sequence (DRS), the independent URS activation produces a small number of mRNA molecules compared to DRS activation. This behavior corresponds to early and later stages of the cell growth, respectively. However, it is probable that in the exponential phase URS and DRS work coordinately in the transcription of the lac operon Sala A, Shoaib M, Anufrieva O, Mutharasu G, Yli-Harja O, Kandhavelu M,2015. Based on the activity of the lac operon, it was determined that many bacterial promoters might be susceptible to similar position-dependent effects, such as the binding of nucleoid-associated proteins to neighboring sequences, supercoiling, and the activity of neighboring promoters, and these factors can affect promoter activity. Like the lac operon, other promoter activities might depend upon the chromosomal location, especially promoters that are located on mobile genetic elements, such as promoters that control the expression of antimicrobial resistance determinants or eve...
Evidence:	[BTEI] Boundaries of transcription experimentally identified [LTED] Length of transcript experimentally determined
Reference(s):	[1] McCormick JR., et al., 1991 [2] Murakawa GJ., et al., 1991
Promoter
Name:	lacZp1
+1:	366343
Sigma Factor:	Sigma70 Sigmulon
Distance from start of the gene:	38
Sequence:	gctcactcattaggcaccccaggctttacactttatgcttccggctcgtatgttgtgtggAattgtgagcggataacaatt -35 -10 +1
Note(s):	lac operon expression was studied during diauxic shift; although it was supposed to be under σ^S control (as σ^S is the main sigma factor for cell adaptation during this change), no σ^S site has been found in this promoter, nor is there a reported correlation of lac expression with σ^S WT or deleted Fischer D, Teich A, Neubauer P, Hengge-Aronis R,1998 Insulation of the lac promoter was tested by Sasson et al. in 2012 Sasson V, Shachrai I, Bren A, Dekel E, Alon U,2012 In that study, activators showed better insulation at high expression levels and repressors showed better insulation at low expression levels, following Savageau's rule, in which Escherichia coli genes that are needed often in the natural environment tend to be regulated by activators and those genes that are rarely needed are regulated by repressors Savageau MA,1974. Sasson V, Shachrai I, Bren A, Dekel E, Alon U,2012
Evidence:	[ICWHO] [IDA] [TIM]
Reference(s):	[3] Belliveau NM., et al., 2018 [4] Cannistraro VJ., et al., 1985 [5] Czarniecki D., et al., 1997 [6] Huerta AM., et al., 2003 [7] Xiong XF., et al., 1991
Terminator(s)
Type:	rho-independent
Sequence:	gaacttgtagGCCTGATAAGCGCAGCGTATCAGGCaatttttata
Reference(s):	[8] Sung YC., et al., 1988
Type:	rho-independent
Sequence:	gggtcaaagaGGCATGATGCGACGCTTGTTCCTGCGCTTTGTTCATGCCGgatgcggcta
Reference(s):	[9] Hediger MA., et al., 1985

TF binding sites (TFBSs)

[CRP,+] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
proximal	CRP-cyclic-AMP	activator	lacZp1	366322	366343	11.5	tgttgtgtggAATTGTGAGCGGATAACAATTTcacacaggaa	nd	[APIORCISFBSCS], [BPP]	[24], [25], [26]
proximal	CRP-cyclic-AMP	activator	lacZp1	366394	366415	-61.5	gcaacgcaatTAATGTGAGTTAGCTCACTCATtaggcacccc	nd	[GEA], [APIORCISFBSCS], [BPP], [SM]	[3], [5], [7], [15], [16], [17], [18], [19], [20]

[H-NS,-] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
proximal	H-NS	repressor	lacZp1	366313	366327	24.0	gagcggataaCAATTTCACACAGGAaacagctatg	nd	[BPP]	[13], [14]
proximal	H-NS	repressor	lacZp1	366331	366345	6.0	tatgttgtgtGGAATTGTGAGCGGAtaacaatttc	nd	[BPP]	[13], [14]
proximal	H-NS	repressor	lacZp1	366341	366355	-5.0	ttccggctcgTATGTTGTGTGGAATtgtgagcgga	nd	[BPP]	[13], [14]
proximal	H-NS	repressor	lacZp1	366367	366381	-31.0	ggcaccccagGCTTTACACTTTATGcttccggctc	nd	[BPP]	[13], [14]
proximal	H-NS	repressor	lacZp1	366390	366404	-54.0	aatgtgagttAGCTCACTCATTAGGcaccccaggc	nd	[BPP]	[13], [14]
proximal	H-NS	repressor	lacZp1	366403	366417	-67.0	gcgcaacgcaATTAATGTGAGTTAGctcactcatt	nd	[BPP]	[13], [14]

[LacI,-] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
remote	LacI	repressor	lacZp1	365922	365942	412.0	gaatccgacgGGTTGTTACTCGCTCACATTTaatgttgatg	nd	[APIORCISFBSCS], [GS], [SM]	[10], [11], [12]
proximal	LacI	repressor	lacZp1	366323	366343	11.0	tgttgtgtggAATTGTGAGCGGATAACAATTtcacacagga	nd	[GEA], [APIORCISFBSCS], [BPP], [GS], [SM]	[3], [12], [22], [23]
proximal	LacI	repressor	lacZp1	366415	366435	-82.0	ctggaaagcgGGCAGTGAGCGCAACGCAATTaatgtgagtt	nd	[APIORCISFBSCS], [GS], [SM]	[10], [11], [12]

[MarA,-] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
proximal	MarA	repressor	lacZp1	366366	366381	-30.0	ggcaccccagGCTTTACACTTTATGCttccggctcg	nd	[GEA], [BPP], [SM]	[21]

Transcription factor	Function	Promoter	Binding Sites	Evidence (Confirmed, Strong, Weak)	Reference(s)
LacI	repressor	lacZp1	366415	366435	-82.0	ctggaaagcgGGCAGTGAGCGCAACGCAATTaatgtgagtt	nd	[10], [11], [12]
H-NS	repressor	lacZp1	366403	366417	-67.0	gcgcaacgcaATTAATGTGAGTTAGctcactcatt	nd	[13], [14]
CRP-cyclic-AMP	activator	lacZp1	366394	366415	-61.5	gcaacgcaatTAATGTGAGTTAGCTCACTCATtaggcacccc	[GEA]	[3], [5], [7], [15], [16], [17], [18], [19], [20]
H-NS	repressor	lacZp1	366390	366404	-54.0	aatgtgagttAGCTCACTCATTAGGcaccccaggc	nd	[13], [14]
H-NS	repressor	lacZp1	366367	366381	-31.0	ggcaccccagGCTTTACACTTTATGcttccggctc	nd	[13], [14]
MarA	repressor	lacZp1	366366	366381	-30.0	ggcaccccagGCTTTACACTTTATGCttccggctcg	[GEA]	[21]
H-NS	repressor	lacZp1	366341	366355	-5.0	ttccggctcgTATGTTGTGTGGAATtgtgagcgga	nd	[13], [14]
H-NS	repressor	lacZp1	366331	366345	6.0	tatgttgtgtGGAATTGTGAGCGGAtaacaatttc	nd	[13], [14]
LacI	repressor	lacZp1	366323	366343	11.0	tgttgtgtggAATTGTGAGCGGATAACAATTtcacacagga	[GEA]	[3], [12], [22], [23]
CRP-cyclic-AMP	activator	lacZp1	366322	366343	11.5	tgttgtgtggAATTGTGAGCGGATAACAATTTcacacaggaa	nd	[24], [25], [26]
H-NS	repressor	lacZp1	366313	366327	24.0	gagcggataaCAATTTCACACAGGAaacagctatg	nd	[13], [14]
LacI	repressor	lacZp1	365922	365942	412.0	gaatccgacgGGTTGTTACTCGCTCACATTTaatgttgatg	nd	[10], [11], [12]

Transcription unit

Name:	lacZYA
Synonym(s):	lacZ
Gene(s):	lacA, lacY, lacZ Genome Browser M3D Gene expression COLOMBOS
Note(s):	The lac operon is controlled by four promoters, P1, which is the principal promoter, P2, and P3 and P4, the weaker promoters Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991 Transcription of this operon is both negatively and positively regulated. Negative regulation occurs when the lac repressor (LacI) binds to the operator, preventing transcription by RNA polymerase Schmitz A.,1981. Hudson JM,1990 Positive regulation is mediated by the cAMP receptor protein, CRP (also referred to as the catabolite activator protein, CAP) Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991. Liu M,2004 In the presence of glucose, lac operon expression is not needed and a control mechanism known as catabolite repression occurs. This refers to the ability of glucose to inhibit expression of the operon. As cellular cAMP levels drop in response to glucose uptake, CRP is not activated and operon expression is inhibited. Under this mechanism, lac genes are only expressed if lactose is present and glucose is absent. In the absence of glucose, the levels of cAMP increase and this metabolite binds to CRP. CRP becomes active and it binds to DNA near the lac promoter, facilitating transcription Schmitz A.,1981. Hudson JM,1990 Synthesis of the lac operon proteins is induced when E. coli is grown on lactose in the absence of glucose. CRP is the principal activator of the lac operon. CRP interacts with RNA polymerase and stimulates transcription of lacZp1 by increasing the binding of the RNA polymerase and the open complex stabilization Liu M,2003. Savery N,1996. Noel RJ,1998. In the same way, CRP completely overlaps lacZp2 and lacZp3, avoiding RNA polymerase binding and preventing transcription of these promoters Hudson JM,1990. Eschenlauer AC, Reznikoff WS,1991. Xiong XF,1991 On the other hand, in the absence of allolactose, the LacI repressor represses the lac operon Hudson JM,1990. Lewis M.,2005 In this repression system, LacI binds to two operators centered at positions 10 bp (O1) and -82 bp (O3), and formation of the repressor loop is critical Fried MG, Hudson JM,1996. Perros M, Steitz TA,1996. Balaeff A, Mahadevan L, Schulten K,2004. Hudson JM,1990 Expression of p1 is also stimulated when LacI binds to O1 Hudson JM,1990 Induction occurs when the physiological inducer, allolactose, binds to the lac repressor, preventing it from binding to the operator Hudson JM,1990. Lewis M.,2005 Nonphysiological analogs, such as thiogalactosides, can function as inducers too. Activation of the lac operon can also be partly increased by CRP when it overlaps the O1 site, acting as an antirepressor Straney SB, Crothers DM,1987. Hudson JM,1990 The expression of the lac operon is differently regulated in many strains of E. coli Phillips KN, Widmann S, Lai HY, Nguyen J, Ray JCJ, Balázsi G, Cooper TF,2019.
Evidence:	[ITCR] Inferred through co-regulation [LTED] Length of transcript experimentally determined
Reference(s):	[1] McCormick JR., et al., 1991 [2] Murakawa GJ., et al., 1991
Promoter
Name:	lacZp3
+1:	366358
Distance from start of the gene:	53
Sequence:	aattaatgtgagttagctcactcattaggcaccccaggctttacactttatgcttccggcTcgtatgttgtgtggaattgt
Evidence:	[TIM]
Reference(s):	[5] Czarniecki D., et al., 1997 [7] Xiong XF., et al., 1991
Terminator(s)
Type:	rho-independent
Sequence:	gaacttgtagGCCTGATAAGCGCAGCGTATCAGGCaatttttata
Reference(s):	[8] Sung YC., et al., 1988
Type:	rho-independent
Sequence:	gggtcaaagaGGCATGATGCGACGCTTGTTCCTGCGCTTTGTTCATGCCGgatgcggcta
Reference(s):	[9] Hediger MA., et al., 1985

TF binding sites (TFBSs)

[CRP,-] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
proximal	CRP-cyclic-AMP	repressor	lacZp3	366322	366343	26.5	tgttgtgtggAATTGTGAGCGGATAACAATTTcacacaggaa	nd	[APIORCISFBSCS], [BPP]	[24], [25], [26]
proximal	CRP-cyclic-AMP	repressor	lacZp3	366394	366415	-46.5	gcaacgcaatTAATGTGAGTTAGCTCACTCATtaggcacccc	nd	[GEA], [APIORCISFBSCS], [BPP], [SM]	[3], [5], [7], [15], [16], [17], [18], [19], [20]

Transcription factor	Function	Promoter	Binding Sites	Evidence (Confirmed, Strong, Weak)	Reference(s)
CRP-cyclic-AMP	repressor	lacZp3	366394	366415	-46.5	gcaacgcaatTAATGTGAGTTAGCTCACTCATtaggcacccc	[GEA]	[3], [5], [7], [15], [16], [17], [18], [19], [20]
CRP-cyclic-AMP	repressor	lacZp3	366322	366343	26.5	tgttgtgtggAATTGTGAGCGGATAACAATTTcacacaggaa	nd	[24], [25], [26]

Transcription unit

Name:	lacZYA
Gene(s):	lacA, lacY, lacZ Genome Browser M3D Gene expression COLOMBOS
Note(s):	The lac operon is controlled by four promoters, P1, which is the principal promoter, P2, and P3 and P4, the weaker promoters Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991 Transcription of this operon is both negatively and positively regulated. Negative regulation occurs when the lac repressor (LacI) binds to the operator, preventing transcription by RNA polymerase Schmitz A.,1981. Hudson JM,1990 Positive regulation is mediated by the cAMP receptor protein, CRP (also referred to as the catabolite activator protein, CAP) Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991. Liu M,2004 In the presence of glucose, lac operon expression is not needed and a control mechanism known as catabolite repression occurs. This refers to the ability of glucose to inhibit expression of the operon. As cellular cAMP levels drop in response to glucose uptake, CRP is not activated and operon expression is inhibited. Under this mechanism, lac genes are only expressed if lactose is present and glucose is absent. In the absence of glucose, the levels of cAMP increase and this metabolite binds to CRP. CRP becomes active and it binds to DNA near the lac promoter, facilitating transcription Schmitz A.,1981. Hudson JM,1990 Synthesis of the lac operon proteins is induced when E. coli is grown on lactose in the absence of glucose. CRP is the principal activator of the lac operon. CRP interacts with RNA polymerase and stimulates transcription of lacZp1 by increasing the binding of the RNA polymerase and the open complex stabilization Liu M,2003. Savery N,1996. Noel RJ,1998. In the same way, CRP completely overlaps lacZp2 and lacZp3, avoiding RNA polymerase binding and preventing transcription of these promoters Hudson JM,1990. Eschenlauer AC, Reznikoff WS,1991. Xiong XF,1991 On the other hand, in the absence of allolactose, the LacI repressor represses the lac operon Hudson JM,1990. Lewis M.,2005 In this repression system, LacI binds to two operators centered at positions 10 bp (O1) and -82 bp (O3), and formation of the repressor loop is critical Fried MG, Hudson JM,1996. Perros M, Steitz TA,1996. Balaeff A, Mahadevan L, Schulten K,2004. Hudson JM,1990 Expression of p1 is also stimulated when LacI binds to O1 Hudson JM,1990 Induction occurs when the physiological inducer, allolactose, binds to the lac repressor, preventing it from binding to the operator Hudson JM,1990. Lewis M.,2005 Nonphysiological analogs, such as thiogalactosides, can function as inducers too. Activation of the lac operon can also be partly increased by CRP when it overlaps the O1 site, acting as an antirepressor Straney SB, Crothers DM,1987. Hudson JM,1990 The expression of the lac operon is differently regulated in many strains of E. coli Phillips KN, Widmann S, Lai HY, Nguyen J, Ray JCJ, Balázsi G, Cooper TF,2019.
Evidence:	[ITCR] Inferred through co-regulation [LTED] Length of transcript experimentally determined
Reference(s):	[1] McCormick JR., et al., 1991 [2] Murakawa GJ., et al., 1991
Promoter
Name:	lacZp2
+1:	366365
Distance from start of the gene:	60
Sequence:	gcaacgcaattaatgtgagttagctcactcattaggcaccccaggctttacactttatgcTtccggctcgtatgttgtgtg
Evidence:	[TIM]
Reference(s):	[5] Czarniecki D., et al., 1997 [7] Xiong XF., et al., 1991
Terminator(s)
Type:	rho-independent
Sequence:	gaacttgtagGCCTGATAAGCGCAGCGTATCAGGCaatttttata
Reference(s):	[8] Sung YC., et al., 1988
Type:	rho-independent
Sequence:	gggtcaaagaGGCATGATGCGACGCTTGTTCCTGCGCTTTGTTCATGCCGgatgcggcta
Reference(s):	[9] Hediger MA., et al., 1985

TF binding sites (TFBSs)

[CRP,-] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
remote	CRP-cyclic-AMP	repressor	lacZp2	366322	366343	33.5	tgttgtgtggAATTGTGAGCGGATAACAATTTcacacaggaa	nd	[APIORCISFBSCS], [BPP]	[24], [25], [26]
proximal	CRP-cyclic-AMP	repressor	lacZp2	366394	366415	-39.5	gcaacgcaatTAATGTGAGTTAGCTCACTCATtaggcacccc	nd	[GEA], [APIORCISFBSCS], [BPP], [SM]	[3], [5], [7], [15], [16], [17], [18], [19], [20]

Transcription factor	Function	Promoter	Binding Sites	Evidence (Confirmed, Strong, Weak)	Reference(s)
CRP-cyclic-AMP	repressor	lacZp2	366394	366415	-39.5	gcaacgcaatTAATGTGAGTTAGCTCACTCATtaggcacccc	[GEA]	[3], [5], [7], [15], [16], [17], [18], [19], [20]
CRP-cyclic-AMP	repressor	lacZp2	366322	366343	33.5	tgttgtgtggAATTGTGAGCGGATAACAATTTcacacaggaa	nd	[24], [25], [26]

Transcription unit

Name:	lacZYA
Gene(s):	lacA, lacY, lacZ Genome Browser M3D Gene expression COLOMBOS
Note(s):	The lac operon is controlled by four promoters, P1, which is the principal promoter, P2, and P3 and P4, the weaker promoters Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991 Transcription of this operon is both negatively and positively regulated. Negative regulation occurs when the lac repressor (LacI) binds to the operator, preventing transcription by RNA polymerase Schmitz A.,1981. Hudson JM,1990 Positive regulation is mediated by the cAMP receptor protein, CRP (also referred to as the catabolite activator protein, CAP) Xiong XF,1991. Eschenlauer AC, Reznikoff WS,1991. Liu M,2004 In the presence of glucose, lac operon expression is not needed and a control mechanism known as catabolite repression occurs. This refers to the ability of glucose to inhibit expression of the operon. As cellular cAMP levels drop in response to glucose uptake, CRP is not activated and operon expression is inhibited. Under this mechanism, lac genes are only expressed if lactose is present and glucose is absent. In the absence of glucose, the levels of cAMP increase and this metabolite binds to CRP. CRP becomes active and it binds to DNA near the lac promoter, facilitating transcription Schmitz A.,1981. Hudson JM,1990 Synthesis of the lac operon proteins is induced when E. coli is grown on lactose in the absence of glucose. CRP is the principal activator of the lac operon. CRP interacts with RNA polymerase and stimulates transcription of lacZp1 by increasing the binding of the RNA polymerase and the open complex stabilization Liu M,2003. Savery N,1996. Noel RJ,1998. In the same way, CRP completely overlaps lacZp2 and lacZp3, avoiding RNA polymerase binding and preventing transcription of these promoters Hudson JM,1990. Eschenlauer AC, Reznikoff WS,1991. Xiong XF,1991 On the other hand, in the absence of allolactose, the LacI repressor represses the lac operon Hudson JM,1990. Lewis M.,2005 In this repression system, LacI binds to two operators centered at positions 10 bp (O1) and -82 bp (O3), and formation of the repressor loop is critical Fried MG, Hudson JM,1996. Perros M, Steitz TA,1996. Balaeff A, Mahadevan L, Schulten K,2004. Hudson JM,1990 Expression of p1 is also stimulated when LacI binds to O1 Hudson JM,1990 Induction occurs when the physiological inducer, allolactose, binds to the lac repressor, preventing it from binding to the operator Hudson JM,1990. Lewis M.,2005 Nonphysiological analogs, such as thiogalactosides, can function as inducers too. Activation of the lac operon can also be partly increased by CRP when it overlaps the O1 site, acting as an antirepressor Straney SB, Crothers DM,1987. Hudson JM,1990 The expression of the lac operon is differently regulated in many strains of E. coli Phillips KN, Widmann S, Lai HY, Nguyen J, Ray JCJ, Balázsi G, Cooper TF,2019.
Evidence:	[ITCR] Inferred through co-regulation [LTED] Length of transcript experimentally determined
Reference(s):	[1] McCormick JR., et al., 1991 [2] Murakawa GJ., et al., 1991
Promoter
Name:	lacZp4
+1:	366377
Distance from start of the gene:	72
Sequence:	cgggcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggcttTacactttatgcttccggctc
Evidence:	[TIM]
Reference(s):	[5] Czarniecki D., et al., 1997 [7] Xiong XF., et al., 1991
Terminator(s)
Type:	rho-independent
Sequence:	gaacttgtagGCCTGATAAGCGCAGCGTATCAGGCaatttttata
Reference(s):	[8] Sung YC., et al., 1988
Type:	rho-independent
Sequence:	gggtcaaagaGGCATGATGCGACGCTTGTTCCTGCGCTTTGTTCATGCCGgatgcggcta
Reference(s):	[9] Hediger MA., et al., 1985

Transcription unit

Name:	lacYA
Gene(s):	lacA, lacY Genome Browser M3D Gene expression COLOMBOS
Evidence:	[BTEI] Boundaries of transcription experimentally identified [PAGTSBP] Products of adjacent genes in the same biological process
Reference(s):	[27] Zaslaver A., et al., 2006
Promoter
Name:	lacYp
+1:	Unknown
Note(s):	Zaslaver et al. demonstrated in 2006, by means of a library of fluorescent transcription fusions, that this promoter can be transcribed in vitro Zaslaver A,2006. Based on this, a putative promoter was suggested, but the +1 site of the transcription initiation has not been determined, although there exists promoter activity.
Evidence:	[IEP]
Reference(s):	[27] Zaslaver A., et al., 2006
Terminator(s)
Type:	rho-independent
Sequence:	gaacttgtagGCCTGATAAGCGCAGCGTATCAGGCaatttttata
Reference(s):	[8] Sung YC., et al., 1988
Type:	rho-independent
Sequence:	gggtcaaagaGGCATGATGCGACGCTTGTTCCTGCGCTTTGTTCATGCCGgatgcggcta
Reference(s):	[9] Hediger MA., et al., 1985

RNA cis-regulatory element

Regulation, transcriptional elongation
Attenuator type:	Translational
Strand:	reverse
Evidence:	[ICA] Inferred by computational analysis
Reference(s):	[28] Merino E, et al., 2005

	Structure type	Energy	LeftPos	RightPos	Sequence (RNA-strand)
	terminator	-15.8	366315	366351	ggctcgtatgTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAggaaacagct

Notes: "The provided "Sequence" is that of the RNA strand, i.e. U's are shown instead of T's and regulators on the reverse strand will appear as the reverse complement of the sequence delimited by LeftPos-RigtPos"

Evidence
[ICWHO] Inferred computationally without human oversight
[IDA] Inferred from direct assay
[TIM] Transcription initiation mapping
[APIORCISFBSCS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.
[BPP] Binding of purified proteins
[GEA] Gene expression analysis
[SM] Site mutation
[GS] genomic SELEX
[IEP] Inferred from expression pattern

Reference(s)
[1] McCormick JR., Zengel JM., Lindahl L., 1991, Intermediates in the degradation of mRNA from the lactose operon of Escherichia coli., Nucleic Acids Res 19(10):2767-76
[2] Murakawa GJ., Kwan C., Yamashita J., Nierlich DP., 1991, Transcription and decay of the lac messenger: role of an intergenic terminator., J Bacteriol 173(1):28-36
[3] Belliveau NM., Barnes SL., Ireland WT., Jones DL., Sweredoski MJ., Moradian A., Hess S., Kinney JB., Phillips R., 2018, Systematic approach for dissecting the molecular mechanisms of transcriptional regulation in bacteria., Proc Natl Acad Sci U S A 115(21):E4796-E4805
[4] Cannistraro VJ., Kennell D., 1985, The 5' ends of Escherichia coli lac mRNA., J Mol Biol 182(2):241-8
[5] Czarniecki D., Noel RJ., Reznikoff WS., 1997, The -45 region of the Escherichia coli lac promoter: CAP-dependent and CAP-independent transcription., J Bacteriol 179(2):423-9
[6] Huerta AM., Collado-Vides J., 2003, Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals., J Mol Biol 333(2):261-78
[7] Xiong XF., de la Cruz N., Reznikoff WS., 1991, Downstream deletion analysis of the lac promoter., J Bacteriol 173(15):4570-7
[8] Sung YC., Fuchs JA., 1988, Characterization of the cyn operon in Escherichia coli K12., J Biol Chem 263(29):14769-75
[9] Hediger MA., Johnson DF., Nierlich DP., Zabin I., 1985, DNA sequence of the lactose operon: the lacA gene and the transcriptional termination region., Proc Natl Acad Sci U S A 82(19):6414-8
[10] Flashner Y., Gralla JD., 1988, Dual mechanism of repression at a distance in the lac operon., Proc Natl Acad Sci U S A 85(23):8968-72
[11] Oehler S., Eismann ER., Kramer H., Muller-Hill B., 1990, The three operators of the lac operon cooperate in repression., EMBO J 9(4):973-9
[12] Shimada T., Ogasawara H., Ishihama A., 2018, Single-target regulators form a minor group of transcription factors in Escherichia coli K-12., Nucleic Acids Res 46(8):3921-3936
[13] Rimsky S., Spassky A., 1990, Sequence determinants for H1 binding on Escherichia coli lac and gal promoters., Biochemistry 29(15):3765-71
[14] Spassky A., Rimsky S., Garreau H., Buc H., 1984, H1a, an E. coli DNA-binding protein which accumulates in stationary phase, strongly compacts DNA in vitro., Nucleic Acids Res 12(13):5321-40
[15] Liu M., Garges S., Adhya S., 2004, lacP1 promoter with an extended -10 motif. Pleiotropic effects of cyclic AMP protein at different steps of transcription initiation., J Biol Chem 279(52):54552-7
[16] Liu M., Gupte G., Roy S., Bandwar RP., Patel SS., Garges S., 2003, Kinetics of transcription initiation at lacP1. Multiple roles of cyclic AMP receptor protein., J Biol Chem 278(41):39755-61
[17] Meiklejohn AL., Gralla JD., 1985, Entry of RNA polymerase at the lac promoter., Cell 43(3 Pt 2):769-76
[18] Merkel TJ., Nelson DM., Brauer CL., Kadner RJ., 1992, Promoter elements required for positive control of transcription of the Escherichia coli uhpT gene., J Bacteriol 174(9):2763-70
[19] Noel RJ., Reznikoff WS., 1998, CAP, the -45 region, and RNA polymerase: three partners in transcription initiation at lacP1 in Escherichia coli., J Mol Biol 282(3):495-504
[20] Tutar Y., Harman JG., 2006, Effect of salt bridge on transcription activation of CRP-dependent lactose operon in Escherichia coli., Arch Biochem Biophys 453(2):217-23
[21] Lankester A., Ahmed S., Lamberte LE., Kettles RA., Grainger DC., 2019, The Escherichia coli multiple antibiotic resistance activator protein represses transcription of the lac operon., Biochem Soc Trans 47(2):671-677
[22] Lewis M., 2005, The lac repressor., C R Biol 328(6):521-48
[23] Rastinejad F., Artz P., Lu P., 1993, Origin of the asymmetrical contact between lac repressor and lac operator DNA., J Mol Biol 233(3):389-99
[24] Hudson JM., Fried MG., 1991, The binding of cyclic AMP receptor protein to two lactose promoter sites is not cooperative in vitro., J Bacteriol 173(1):59-66
[25] Hudson JM., Fried MG., 1990, Co-operative interactions between the catabolite gene activator protein and the lac repressor at the lactose promoter., J Mol Biol 214(2):381-96
[26] Schmitz A., 1981, Cyclic AMP receptor proteins interacts with lactose operator DNA., Nucleic Acids Res 9(2):277-92
[27] Zaslaver A., Bren A., Ronen M., Itzkovitz S., Kikoin I., Shavit S., Liebermeister W., Surette MG., Alon U., 2006, A comprehensive library of fluorescent transcriptional reporters for Escherichia coli., Nat Methods 3(8):623-8
[28] Merino E, Yanofsky C., 2005, Transcription attenuation: a highly conserved regulatory strategy used by bacteria., Trends Genet. 2005 May;21(5):260-4.

RegulonDB