Part II-E Regulation Expression Eukaryotes (Exam 2)

Resilience

• A depiction of a person slumped on the ground, surrounded by scattered items, is used to illustrate what resilience might look like.

PART II-E: Control of Gene Expression (Eukaryotes)

• Gene regulation in eukaryotes occurs at multiple levels, impacting various stages.

Regulation of Gene Expression

• Regulation occurs at these levels:
  • Genome/chromatin structure
  • Epigenetic profile and imprinting
  • Transcriptional regulation
  • Post-transcriptional regulation
  • Regulation of Translation
  • Regulation via non-coding RNAs (ncRNAs).

Genome and Chromatin Structure

• Euchromatin and heterochromatin:
  • Transcription occurs in euchromatic DNA.
  • CTCF defines boundaries between euchromatic and heterochromatic regions.
• Chromosome territories:
  • Regions closer to the nuclear envelope are often silenced.
  • TADs (Topologically Associating Domains):
    • Different cell types have unique active/inactive TAD profiles.
• ncRNAs (non-coding RNAs):
  • Bind DNA and proteins involved in DNA/RNA binding.
  • Located in scaffolding complexes affecting chromatin structure.
  • Can recruit chromatin remodeling complexes.

Epigenetic Profile and Imprinting

• Epigenetic mechanisms:
  • Histone modifications
  • Nucleosome positioning
  • DNA methylation
• Chromatin structure is closely linked to the epigenetic profile.
• Epigenetic code:
  • Chemical modifications on histones create chromatin states with varying transcription levels.
  • Chromatin-binding proteins recognize epigenetic marks to establish open/closed chromatin.

DNA Methylation (5-meC of CpG)

• Associated with transcriptional repression.
• Transcription factors cannot bind methylated DNA.
• Specific proteins bind methylated DNA for chromatin organization and epigenetic maintenance.
• Epigenetic memory is maintained through mitosis.
• CpG islands in gene-rich regions are typically unmethylated.
• During gametogenesis, the epigenome resets to a totipotent state.
• Imprinting:
  • Approximately 150 human genes are imprinted.
  • Differential expression from maternal/paternal chromosomes.
  • Methylation of maternal DMR is a common mechanism for imprinting.

Transcriptional Regulation

• Nucleosome positioning:
  • Promoters lack nucleosomes during transcription initiation complex (PIC) assembly.
  • Chromatin remodeling complexes are involved.
• Promoters:
  • About half of mammalian genes have alternative promoters.
• Enhancers:
  • Involved in cell- and tissue-specific gene expression.
  • DNA interactions (cohesin, mediator proteins) are crucial.
  • TAD structure facilitates interactions.

Transcription Factors and the Epigenetic Landscape

• A variety of general and tissue-specific transcription factors govern development and expression.
• Cell differentiation is accompanied by increasing epigenetic restriction.

Regulation of Translation

• Leader peptides:
  • About a third of human transcripts include upstream open reading frames (uORFs).
• mRNA structure:
  • Stem-loop structures affect ribosome movement.
  • RNA-binding proteins bind to mRNA.
• ncRNAs (non-coding RNAs):
  • miRNAs, siRNAs, and piRNAs can repress target mRNA expression.
  • miRNAs bind to 3' untranslated regions (UTRs) to modulate translation rates.
  • miRNAs can compete for target mRNAs (regulating networks of moderate effects).

Additional topics

• X-inactivation is an epigenetic process in early embryogenesis, balancing the expression of X-linked genes. There is random X inactivation in the blastula.
• XIC: X inactivation center (1 Mb)
• 19 Kb ncRNA: (X inactivation specific transcript) is abundant in the chromosome slated to be inactivated.
• Y chromosome (Protein-coding genes): contains approximately 45 protein-coding genes, whereas the X chromosome has 1,000-2,000 protein-coding genes.
• Post-transcriptional regulation:
  • Alternative splicing is regulated by splicing enhancers/suppressors, producing strong or weak splice sites based on tissue type.
  • Impacts include sub-cellular compartment signals, transmembrane domains, and modification of proteins.
  • RNA turnover and RNA editing processes.