Gene Regulation Mechanisms

Overview

This lecture focuses on the lactose operon and epigenetic regulation of gene expression, comparing prokaryotic and eukaryotic mechanisms.

The lactose operon (lac operon) allows bacteria to metabolize lactose when glucose is scarce.
It includes genes encoding enzymes for lactose uptake and metabolism.
When glucose is low, cyclic AMP (cAMP) accumulates and binds to catabolite activator protein (CAP).
The cAMP-CAP complex binds the promoter, stabilizing RNA polymerase, increasing transcription of lactose metabolism genes.
The lac operon is an inducible operon, usually off unless lactose is available.
The lac repressor binds the operator and blocks transcription when lactose is absent.
Lactose acts as an inducer, binding to the repressor and preventing it from binding the operator, allowing transcription.
High transcription of the lac operon occurs only when lactose is present and glucose is low (high cAMP-CAP).
If lactose is absent, transcription does not occur, regardless of glucose levels.

The trp operon is "on" by default to produce tryptophan, a necessary amino acid, but is repressed when tryptophan is abundant.
The lac operon is "off" by default and only activated in the presence of lactose and absence of glucose.

Eukaryotic gene expression is more complex due to the nucleus and multiple regulatory levels.
Epigenetic regulation controls DNA accessibility before transcription.
Chromatin remodeling involves how tightly DNA is wound around histones, affecting gene accessibility.
DNA methylation (addition of methyl groups) typically silences genes by tightening DNA-histone interactions.
Histone acetylation (addition of acetyl groups) loosens DNA-histone interactions, enhancing gene expression.
These modifications are known as chemical tags and can be reversible, influenced by environment and diet.
Direct methylation of DNA in CpG islands (promoter regions) also silences genes and can be heritable (imprinted genes).
Epigenetic changes can result from development, environment, aging, or stress and may contribute to diseases.

Operon — a cluster of genes transcribed as a single mRNA in prokaryotes.
Inducible operon — an operon that is usually off but can be turned on by an inducer.
Repressor — a protein that binds to an operator to prevent gene transcription.
cAMP (cyclic AMP) — a signaling molecule that accumulates when glucose is low.
CAP (catabolite activator protein) — binds with cAMP to increase transcription.
Epigenetics — regulation of gene expression without altering DNA sequence.
Chromatin remodeling — changes in DNA-histone interactions affecting gene accessibility.
DNA methylation — addition of methyl groups to DNA, usually silencing genes.
Histone acetylation — addition of acetyl groups to histones, increasing gene expression.
CpG island — DNA regions with high cytosine and guanine content, often in gene promoters.

Review the table of conditions that regulate lac operon transcription.
Prepare for the next lecture on eukaryotic transcription and gene regulation mechanisms.
Reread textbook sections on operon regulation and epigenetic modifications.