Although almost all cells contain the same DNA, they express different proteins depending on cell type and environmental conditions. Understanding mechanisms that regulate gene expression is essential for understanding development, differentiation, and disease.
Basic Knowledge
Gene-expression regulation in prokaryotes: the lac operon (Jacob and Monod, 1961): An operon consists of a promoter+operator+group of structural genes. A repressor binds to the operator → RNA polymerase is inhibited → transcription OFF. Lactose (the inducer derivative is allolactose) binds to the repressor → the repressor changes shape → it dissociates from the operator → transcription ON. Catabolite repression (CAP): low glucose → cAMP↑ → CAP activation → transcription promotion.
Gene-expression regulation in eukaryotes: ① Transcription factors have DNA-binding and activation domains and bind to enhancers or promoters to promote or inhibit transcription. ② Chromatin-structure regulation: histone modification (acetylation → transcription activation; methylation → transcription repression) and DNA methylation (CpG methylation → transcription repression) are forms of epigenetics. ③ miRNA/siRNA: RNA interference (RNAi) through mRNA degradation and translation inhibition.
Development and gene expression: Homeotic genes (Hox genes) in fruit flies determine the identity of body segments along the anterior-posterior axis. Hox genes are conserved in nearly all multicellular animals and are evolutionarily important.
Explain the expression state of the lac operon in Escherichia coli when glucose is present and lactose is absent.
Answer: Because allolactose (the inducer) is absent, the repressor remains bound to the operator → RNA polymerase is inhibited and transcription of the lac genes is OFF. In addition, when glucose is present, cAMP is low and CAP is inactive, so transcription is not promoted. For both reasons, the lac genes are not transcribed (glucose is used preferentially).
- Operon = promoter+operator+group of structural genes
- Repressor = binds to the operator and inhibits transcription
- Inducer (allolactose) = inactivates the repressor
- Transcription factor = binds to enhancers and promoters to regulate transcription
- Histone acetylation = transcription activation; methylation = repression
- DNA methylation (epigenetics) = transcription repression
- miRNA/RNAi = mRNA degradation and translation inhibition
Points to Note
① An operon is a regulatory unit in prokaryotes and is not common in eukaryotes, which generally have a promoter for each gene. ② Epigenetic changes (DNA methylation and histone modification) are inherited by cells after division, but the base sequence does not change. ③ The homeodomain of a Hox gene is a DNA-binding domain that regulates downstream groups of genes as a transcription factor.
Practice
- Explain how transcription is regulated in the lac operon when lactose is present and glucose is absent.
- Explain how histone acetylation activates transcription in terms of changes in chromatin structure.
- Explain RNA interference (RNAi), including the action of miRNA.