Gene Regulation in Eukaryotes

Gene Regulation in Eukaryotes

• Eukaryotic gene expression is controlled through multiple mechanisms, including transcription, mRNA processing, transport, storage, translation, and protein modification.
• Unique features of eukaryotic cells, such as increased DNA content and histone interactions, enhance gene regulation.

Mechanisms of Gene Regulation

• mRNAs undergo splicing, capping, and polyadenylation, with each step subject to regulation.
• Eukaryotic mRNAs exhibit varied half-lives, enabling adaptive responses to environmental changes.
• Translation rates and post-translational protein processing can be modified for further control.

Ribosomal RNA

• rRNA genes, essential for ribosome formation, are located on afrocentric chromosomes and clustered in the nucleolus.

Chromatin Structure

• Chromatin is formed by nucleosomes wrapped into 30nm fibers, with histones and nonhistone proteins influencing gene accessibility.
• Nucleosomes have protruding polypeptide tails that can be chemically modified, impacting gene regulation.

Chromosome Organization

• In the interphase nucleus, each chromosome exists in a defined territory, separating it from others.
• Active genes are typically located at the edges of these chromosome territories, adjacent to interchromosomal domains.

Transcription Factories

• Transcription factories are nuclear sites housing RNA polymerase and regulatory molecules, facilitating enhanced gene expression by concentrating necessary factors.

Chromatin States

• Open Chromatin (euchromatin) is loosely bound and accessible to transcription factors, allowing gene expression.
• Closed Chromatin (heterochromatin) is tightly compacted, restricting transcription factor access and inhibiting gene expression.

Chromatin Dynamics

• Both active and inactive genes are associated with nucleosomes, with differences in nucleosome conformation linked to transcriptional activity.

Mechanisms of Chromatin Alteration

• Chromatin can be modified through changes in nucleosome composition, histone modifications, and chromatin remodeling, allowing dynamic regulation of gene expression.

Nucleosome Composition

• Variants like H2A.Z within nucleosomes affect positioning and mobility, influencing gene activation or repression at promoters.

Histone Modifications

• Covalent modifications on histone N-terminal tails can activate or deactivate genes; acetylation and methylation are key processes.
• Acetylation reduces histone-DNA affinity, promoting transcription; catalyzed by HATs and reversed by HDACs.

Methylation Effects

• Histone methylation enhances transcription by favoring euchromatin states.
• DNA methylation, on the other hand, silences genes by adding methyl groups to DNA, often observed in hemizygous states like the inactivated X chromosome in females.