Regulation of Gene Expression

Overview of enhancers and promoters

• multiple per gene

• enhancers differ in places in diff tissues

• TFs are different in diff tissues

How are motifs derived experimentally?

• based on binding to either a polynucleotide (SELEX) or (ChIP-Seq) where the DNA is complexed with histones

Transcription factor classes

based on the DNA binding domain …

How is trabscription factor activity regulated

• transcription factors must be in the nucleus to function, this a common mechanism is regulation of its nuclear or cytoplasmic localization

  • sythesis

  • ligand binding

  • covalent formation

  • regulated nuclear

  • release from a membrane

Synthesis TF regulation

ex. includes c-fos, ERK, and Elk-1

• ERK kinase phosphorylates Elk which inducts the c-phos gene

Elk

• has a DNA binding domain which is normally blocked by another TF

• when elk is phosphorylated it can bind to DNA and its second domain binds to SRF (weak transcription activator) (stabilizes it)

• …

complex formation TF regulation

COvalent modifications causing dimerization TF regukation

Ligand binding TF regukation

Release from membrane TF regulation

sequesters TF outside of nucleus and TF that binding to a DNA binding protein

Histone modifications

• can activiate or repress transcription

• all histones are modified, but much research is done on H3

Histone modification: acetylation

loosens DNA from the histones to increase transcription

• positive charge of lysine is removed

• reduces affinity for negatively charged DNA

Histone Modification: methylation

steric hindrance on lysine and arginine

• does not change charge

• lysine’s can be methylated in different amounts which have different effects/functionality

• assosiation of methylation with transcription and distinct locations within genes

• distinct histone methylations are associated with active and repressed regions

epigenetic processes can be classified into

writers

• putting on the modifications

Erasers

• remove methyl’s and acetyl groups

• histone deacetylases

readers

• binding to the modification and bringing in other proteins for specific functions (ex. chromatin remodeling)

…

Histone ubiquitin

• added to the histone tail

• strong steric effect

Chromatin remodeling

essential for transcription and is one of the methods for regulating efficiency …

Bromo domain: recognizes acetyletes lysines