Eukaryotic Gene regulation

Transcriptional activators

combine dna-binding to a specific site with activation activity

activators are regulators that work on local promoters to increase transcription

enhancers are specific dna sequences that activators can bind to. can act at a long distance (Kbp) from the promoter and in any orientation. their function is often linked to chromatin structure.

insulator elements can isolate enhancers from neighboring genes, preventing unwanted activation.

repressors/silencers are regulators that turn DOWN gene expression. They achieve this by antagonism with an activator or independently.

Androgen (testosterone) receptor (AR)

AR acts like a simple switch.

binds steroid hormone (testosterone) which activates its ability to enter the nucleus, bind DNA, and act as a transcriptional activator.

before hormone binding, the AR is held in the cytoplasm by interaction with hsp90.

binding of the hormone allows the receptor to move to the nucleus and bind DNA at appropriate promoters.

Galactose utilization in yeast

involves several genes that work together

• target genes (structural genes) are GAL1, GAL7, and GAL10, which convert galactose to glucose

• regulatory genes:

  • GAL4: this protein binds DNA and can activate transcription. Achieves this by binding general transcription factors (TFIID & B) directly or indirectly (through SAGA Mediator)

  • GAL80: this protein binds GAL4 and masks GAL4’s activation domain (AD).

  • GAL3: binds galactose.

• in absence of galactose: GAL80 masks the GAL4 activation, reuslting in no transcription of target genes.

• with galactose: GAL3 binds galactose. This GAL3-galactose complex then interacts with GAL80 to remove it from binding to GAL4, therefore no longer masks activation domain, GAL4 is active, transcription occurs.

Chromatin remodeling

changes in the structure of the DNA-protein complex.

often a target of activation domains of transcription factors.

Nucleosome repositioning

moving nucleosomes away from the promoter or binding site

SWI/SNF similar to helicase and creates torsional stress in DNA that moves nucleosomes

Histone variant substitution

diff versions of certain histone proteins can be substituted into a nucleosome

makes that nucleosome easier to move, potentially marking a gene as easily turned on

histone 3.3 or 2B.z found near promoters of active genes. these variant nucleosomes might be looser/more easily displaced

Histone acetylation/deacetylation

acetylation/deacetylation of lysine and arginine residues on histone tails

Acetylation of histone tails

loosens DNA binding and is associated with activate genes

HAT (histone acetylase) is the enzyme that adds acetyl group

Deacetylation of histone tails

tightens interaction and is associated with silenced genes.

HDAC (histone deacetylase) is the enzyme that removes an acetyl group. methylation of deacetylated histones seals in silencing/compaction.