text: Specific control of the lac genes depends on the availability of the substrate lactose to the bacterium. The proteins are not produced by the bacterium when lactose is unavailable as a carbon source.
  The lac genes are organized into an operon; that is, they are oriented in the same direction immediately adjacent on the chromosome and are co-transcribed into a single polycistronic mRNA molecule.  Transcription of all genes starts with the binding of the enzyme RNA polymerase (RNAP), a DNA-binding protein, which binds to a specific DNA binding site, the promoter, immediately upstream of the genes. Binding of RNA polymerase to the promoter is aided by the cAMP-bound catabolite activator protein (CAP, also known as the cAMP receptor protein).  However, the lacI gene (regulatory gene for lac operon) produces a protein that blocks RNAP from binding to the operator of the operon. This protein can only be removed when allolactose binds to it, and inactivates it. The protein that is formed by the lacI gene is known as the lac repressor. The type of regulation that the lac operon undergoes is referred to as negative inducible, meaning that the gene is turned off by the regulatory factor (lac repressor) unless some molecule (lactose) is added. Once the repressor is removed, RNAP then proceeds to transcribe all three genes (lacZYA) into mRNA. Each of the three genes on the mRNA strand has its own Shine-Dalgarno sequence, so the genes are independently translated. The DNA sequence of the E. coli lac operon, the lacZYA mRNA, and the lacI  genes are available from GenBank [https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=146575 (view)].
  The first control mechanism is the regulatory response to lactose, which uses an intracellular regulatory protein called the lactose repressor to hinder production of β-galactosidase in the absence of lactose.  The lacI gene coding for the repressor lies nearby the lac operon and is always expressed (constitutive).  If lactose is missing from the growth medium, the repressor binds very tightly to a short DNA sequence just downstream of the promoter near the beginning of lacZ called the lac operator.  The repressor binding to the operator interferes with binding of RNAP to the promoter, and therefore mRNA encoding LacZ and LacY is only made at very low levels.  When cells are grown in the presence of lactose, however, a lactose metabolite called allolactose, made from lactose by the product of the lacZ gene, binds to the repressor, causing an allosteric shift.  Thus altered, the repressor is unable to bind to the operator, allowing RNAP to transcribe the lac genes and thereby leading to higher levels of the encoded proteins.
  The second control mechanism is a response to glucose, which uses the catabolite activator protein (CAP) homodimer to greatly increase production of β-galactosidase in the absence of glucose. Cyclic adenosine monophosphate (cAMP) is a signal molecule whose prevalence is inversely proportional to that of glucose. It binds to the CAP, which in turn allows the CAP to bind to the CAP binding site (a 16 bp DNA sequence upstream of the promoter on the left in the diagram below, about 60 bp upstream of the transcription start site), which assists the RNAP in binding to the DNA. In the absence of glucose, the cAMP concentration is high and binding of CAP-cAMP to the DNA significantly increases the production of β-galactosidase, enabling the cell to hydrolyse lactose and release galactose and glucose.
  More recently inducer exclusion was shown to block expression of the lac operon when glucose is present.  Glucose is transported into the cell by the PEP-dependent phosphotransferase system.  The phosphate group of phosphoenolpyruvate is transferred via a phosphorylation cascade consisting of the general PTS (phosphotransferase system) proteins HPr and EIA and the glucose-specific PTS proteins EIIA and EIIB, the cytoplasmic domain of the EII glucose transporter.  Transport of glucose is accompanied by its phosphorylation by EIIB, draining the phosphate group from the other PTS proteins, including EIIA.  The unphosphorylated form of EIIA binds to the lac permease and prevents it from bringing lactose into the cell.  Therefore, if both glucose and lactose are present, the transport of glucose blocks the transport of the inducer of the lac operon.