Mar 25, 2025 Eukaryotic Gene Regulation (Epigenetics)

What does “epigenetic” mean? 

  • Epi = “above” or “beyond” 

  • Epigenetic means “above the genes” (layered on top of the DNA sequence) 

  • Epigenetic regulation of transcription involves changes to the packaging of DNA (chromatin), which affects how easily genes can be transcribed

  • Epigenetic states are stable and can be inherited through cell divisions, sometimes across generations, just like genes 

  • However (unlike genes) epigenetic states are often reversible and responsive to changes in the environment

    • Means that life experiences, environment can affect which of our genes get expressed, and we can pass these epigenetic “settings” on to our kids

What is chromatin & what does it have to do with DNA?

  • Packaging of DNA (chromatin) 

  • In nucleus, long stretches of DNA are wound around series of organizing proteins called histones 

  • At this level, organization of DNA (+ histones) resemble beads on a string 

    • Each bead is called a nucleosome, made up of a cluster of histone proteins with DNA strand wound around several times 

  • The string of nucleosomes is further coiled to make a denser fiber of chromatin 

  • Chromatin is what chromosomes are made out of (DNA+histones)

How does chromatin packaging affect gene transcription?

  • For a gene to be transcribed, the DNA must be accessible… 

  • When the chromatin is SUPER coiled and condense, the proteins that carry out transcription cannot access the DNA for that gene 

  • If cell wants to express that gene, chromatin remodeling and unraveling must occur in that region so that transcription factors and RNA polymerase can bind to promoter and/or enhancers for that gene

Keep in mind, epigenetic chromatin remodeling… 

  • Is stable but can be reversed 

  • Can occur in response to the environment

  • Is passed on when a cell divides 

  • Can sometimes be passed through down generations

How is chromatin remodeled? 

  • Two major ways to remodel chromatin 

  1. Chemical changes to histone proteins 

  2. Chemical changes to DNA bases 

How is chromatin remodeled: Histone proteins 

  • Histones have tails (sequence of unfolded amino acids)

  • Acetylating histone tails leads to more open chromatin

  • Histone tails can be acetylated or deacetylated at any given time in response to cell signaling or other environmental conditions 

Common Chemical Modification 

  • The most common chemical modification to DNA is methylating (adding CH3 to) cytosine nucleotide bases

  • Cytosines that get methylated are usually right next to Guanine bases

  • Places (loci) in the DNA where C and G are next to each other called CpG sites

  • Clusters of CpG sites are typically found in the promoter region of a gene 

    • If these CpG sites are methylated, this will decrease gene expression

  • Prevents activating transcription factors from binding

  • Increases repressor binding 

  • Recruits histone modifying enzymes to condense chromatin 

  • Like other epigenetic modifications, CpG methylation can change over time or in response to environmental cues, providing a way to turn gene transcription on or off depending on circumstances