Gene Regulation in Eukaryotes

Study Notes

Gene expression involves accessing information within genes to produce RNA and polypeptides, affecting cellular properties
Gene regulation controls the level of gene expression to maintain optimal levels for cellular function
Eukaryotic gene expression is regulated at various stages of polypeptide synthesis, including transcription (discussed here and in chapter 16), translation (chapters 13 & 17), and post translation (chapters 14 & 23)
Regulatory transcription factors can activate or inhibit transcription
Nucleosome arrangements and composition influence transcription
DNA methylation typically inhibits transcription
Alternative splicing and RNA editing alter RNA sequences

Transcription factors influence RNA polymerase's ability to transcribe DNA into RNA. They regulate the binding of the preinitiation complex, influencing the switch between initiation and elongation
General transcription factors (GTFs) are essential for all transcription, regulating RNA polymerase binding and elongation
Regulatory transcription factors (RTFs) are diverse and regulate transcription rates
RTFs have domains with specific functions, such as DNA binding or interaction with effector molecules
Structural motifs, such as helix-turn-helix, helix-loop-helix, zinc fingers, and leucine zippers, are commonly found in RTFs and allow them to bind to DNA
These domains recognize specific DNA sequences due to complementary biochemical properties and ionic interactions
Enhancers are DNA regions containing regulatory elements that increase or decrease transcription rates when bound to RTFs; these are frequently located some distance from the promoter
Activators bind to enhancers to promote transcription rates, while repressors prevent transcription
Enhancers function bidirectionally
Enhancer location relative to the gene's promoter can vary significantly
Gene regulation involves combinatorial control, where the combined effect of multiple factors determines gene expression

Chromatin remodeling refers to dynamic changes in chromatin structure, affecting DNA accessibility to regulatory elements
Chromatin remodeling complexes, such as SWI/SNF, ISWI, INO80, and Mi-2, use ATP to reposition and restructure nucleosomes
Histone variants have altered amino acid sequences that influence chromatin structure and gene regulation
Histone modifications (acetylation, methylation, and phosphorylation) affect transcription by influencing nucleosome interactions and interactions with other proteins

DNA methylation involves attaching a methyl group to a cytosine base
Full methylation affects transcription by blocking the binding of proteins; hemimethylation occurs when methylation of only one strand has occurred
Methylation commonly occurs at CpG islands near gene promoters
Methylated CpG islands are often correlated with inactive genes
Maintenance methylation ensures the inheritance of DNA methylation patterns during cell division
De novo methylation is the addition of methyl groups to unmethylated DNA