BIOL 331 - Module 4 - Control of Gene Expression and Reprogramming

transcription factor domains

DNA binding domain, transactivation domain, ligand binding domain

DNA binding domain

binds to DNA response elements

transactivation domain

activate transcription

ligand binding domain

sometimes there, bind a molecule to activate the transcription factor

steroid nuclear hormones

• Eg. glucocorticoids, progestins, estrogens, androgens, and mineralocorticoids

• Receptors for these hormones are present in the cytoplasm, bound to chaperone proteins (eg. HSP90)

• Ligand binding results in release of the receptor from the chaperone, homodimerization, and translocation into the nucleus 

  • Activate receptor complex binds the DNA response element and associates with transcriptional coactivators that help activate target genes

glucocorticoid receptor

• a nuclear receptor that includes a ligand-binding domain and a DNA-binding transcription factor

  • Has a zinc-finger motif 

zinc-finger motif

A zinc ion of each finger is coordinated between two cysteines and two histidines

Fingers independently project into successive major grooves in the target DNA  

glucocorticoid response element (GRE)

binds to the glucocorticoid receptor, a palindrome - two DNA strands have the same 5’ to 3’ sequence

transcriptional control

DNA sites involved in regulating transcription

modifications control chromatin state

• DNA/histone methylation —> inhibits

• histone acetylation —> activates

transcriptional activation at the promoter

• Active glucocorticoid receptor (GR) binds DNA and recruits coactivators

• Nucleosome histones are acetylated

• Acetylated histones recruit SWI/SNF (chromatin remodeling complex)

• Transcriptional machinery and polymerase II can bid for RNA transcription 

SWI/SNF chromatin remodelers

Recruited to specific promoters by either epigenetic marks present on nucleosomal histones or other proteins bound to the DNA, thought to disrupt histone-DNA interactions

transcriptional repression

• Repressor recruits a corepressor (eg. HDAC - histone deacetylases) to remove acetyl groups and repress transcription 

  • Recruited to specific gene loci by transcription factors and cause gene silencing 

• A methyltransferase is recruited and methylates K9H3

  • Leads to inactive state of chromatin and gene silencing 

type II nuclear steroid hormone receptors

• Eg. thyroid hormone receptor, retinoic acid receptor

• In the absence of ligand, they are in the nucleus bound to their DNA response elements 

• Gene repression occurs through interactions with NCoR and SMRT corepressor complexes - associated with histone deacetylases (HDACs)

• Ligand binding leads to dissociation of corepressors and their replacement with coactivator complexes and histone acetyltransferases, to open up chromatin and activation of target genes