GN 301 Module 3: Regulation of Gene Expression and Epigenetics

Chromosome Structure and Gene Regulation

  • DNA is complexed with proteins called histones to form chromosomes
  • Chromatin folds and complexes with non-histine proteins to form coiled chromosome
  • ==Modifications of Histones== affect gene expression
  • Histone acetylation
    • increases gene expression since the DNA and histones are less tightly joined

Gene Structure and Function of Components in Transcription

  • Function of ==RNA polymerase==:
    • transcribes and produces the primary transcript
  • Function of ==transcription factors==:
    • bind to the promoter and then allow RNA polymerase to bind

Primary Transcript is processed to form mature mRNA:

  • 5’ cap is added, 3’PolyA Tail is added, introns are removed and exons are joined together

Role of ==Enhancers:==

  • Enhancers are DNA sequences that play an important role in the regulation of gene expression. They are located some distance away from the gene they regulate and can be located upstream or downstream of the gene, or even within an intron. Enhancers can act over long distances and interact with the gene promoter region, which is located upstream of the gene's transcription start site, to modulate transcription of the gene.
  • When a gene is activated, RNA polymerase binds to the promoter and initiates transcription of the gene. Enhancers work by binding to specific transcription factors, which are proteins that bind to DNA and help to regulate gene expression. These transcription factors then interact with the promoter and RNA polymerase to either enhance or inhibit transcription of the gene.
  • The specific combination of enhancers and transcription factors can determine the level of expression of a particular gene in different cell types, at different developmental stages, and in response to different environmental stimuli. Enhancers can act independently or in a cooperative manner with other enhancers to regulate gene expression. This allows for fine-tuned and context-specific regulation of gene expression, which is critical for proper cellular function and development.

What is ==cDNA==? What is it formed from?

  • cDNA (complementary DNA) is DNA formed from active genes, produced by the enzyme reverse transcriptase

Epigenetics

Define Epigenetics:

  • Heritable changes in gene expression that occur without alterations in DNA sequences.

Some inherited epigenetic changes are

  • Methylation of the base cytosine
  • Modifications of histones such as acetylation of the amino acid lysine
    • Acetylation of the amino acid lysine is a type of post-translational modification that can occur on histone proteins, which are the proteins that package DNA into chromatin. This modification involves the addition of an acetyl group (-COCH3) to the lysine residue on a histone protein, and is catalyzed by enzymes called histone acetyltransferases (HATs).
    • Acetylation of lysine residues in histones can have several effects on chromatin structure and gene expression. When lysine residues in histones are acetylated, the positive charge on the lysine is neutralized by the acetyl group, which can weaken the interaction between the positively charged histones and the negatively charged DNA. This can lead to a more relaxed chromatin structure that is more accessible to the transcriptional machinery, which can result in increased gene expression.
    • In addition to its effect on chromatin structure, acetylation of lysine residues can also recruit other proteins to the chromatin that can affect gene expression. For example, the acetyl groups on histones can serve as binding sites for proteins that have specific acetyl-lysine binding domains, such as bromodomain-containing proteins. These proteins can then recruit other proteins to the chromatin, such as transcriptional activators or co-activators, that can further enhance gene expression.

Epigenetic Changes in Astronauts

  • Space did not alter DNA. Gene expression patterns changed for twins about 7% from what they used to be after one of them was in space for a year.