Transcriptional Control of Gene Expression

3 types of eukaryotic RNA polymerase that catalyse TS of genes encoding different classes of RNAs

- RNA pol 1: pre-rRNA - RNA pol 2: protein-coding genes (mRNA) and U-rich snRNA molecules involved in RNA splicing (U1, U2, U4, U5) - RNA pol 3: tRNA, 5S rRNA, U6 (RNA splicing), SRP

Signals & Receptors

- signaling molecules are a chemical released by a signaling cell • also known as *ligands* • signals can be a lipid, gas, proteins, etc. - the signal chemical is recognized by a *receptor* which is a protein in or on the responding cell - ligands and receptors have a very specific fit

2 domains of TS factors

1. N-term DNA-binding domain: binds specific DNA sequences 2. C-term activation or repression domain: interacts w/ other proteins to stimulate or repress TS

Transcriptional control regions

1. Promoters 2. Promotor-proximal elements 3. Distal enhancers

3 types of promoters in eukaryotes

1. TATA box: usually -25 to -35bp from start site, most common 2. Initiator: alternative promoter element, not well defined 3. CpG island: many constitutive genes, TS at low rates

Receptors may be

1. cell surface receptors - hydrophilic signal molecules 2. nuclear receptors - hydrophobic signals

enhancer

A DNA segment containing multiple control elements that can recognize certain transcription factors that stimulate the transcription of nearby genes.

silencer

A eukaryotic DNA sequence that functions to inhibit the start of gene transcription; may act analogously to an enhancer by binding a repressor.

activator

A protein that binds to DNA and stimulates transcription of a specific gene

repressor

A protein that suppresses the transcription of a gene.

Control of Transcription

All cels in an organism have the same genome but all genes are not expressed in all cells

RNA polymerase

Binds to promoter region of DNA and initiates trancription

DNA-binding domains contain many motifs, most common is:

C2H2 Zinc finger

Transcription factors

Collection of proteins that mediate the binding of RNA polymerase and the initiation of transcription.

Promoters

DNA sequence specifying RNA pol binding site, initiates TS of a gene and influences rate of TS

2 types of chromatin

Extended Condensed

Heterodimeric nuclear receptors

In the absence of ligand, heterodimeric receptors are bound to their cognate DNA, direct histone deacetylation & suppress TS

In the presence of (...) there is an increased ardently Cyclades activity, leading to an increase in cAMP

Low glucose

Epigenetics at histones

Methylation and acetylation at the histones

euchromatin

The less condensed form of eukaryotic chromatin that is available for transcription.

Methylation

a biochemical process that influences behavior by suppressing gene activity and expression

Enhancesomes

a higher-order protein complex assembled at the enhancer and regulates expression of a target gene

Eukaryotes control gene expression

at many levels: - control of transcription - control at the level of RNA processing - control at the level of translation - post-translational modification

Prokaryotes control gene expression

at the level of the control of transcription, because there is no mRNA processing

Activator proteins

bind control elements (near initiation site and far away) to promote chromatin decondensation

Repressor proteins

bind different control elements, lead to chromatin condensation

Deacetylation

condenses DNA

The rate of gene expression of identical genes

differs among cells, and in the same cell at different times

Promoter-proximal elements

help regulate eukaryotic genes - control regions lying b/w 100-200bp upstream of start site

DNA-binding domains contain many motifs, others include

homeodomain, basic helix-loop-helix, & leucine zipper

epigenetics at cytosines

methylation at cytosines - genes are to be turned off

Transcription factors

proteins that bind to DNA to stimulate (activators) or inhibit (repressors) transcription

Silencer sequence

regulatory DNA sequences that can repress transcription of specific genes that may be located distantly from the sequence

Acetylation

relaxes the condensation of DNA

RNA polymerase

responsible for RNA synthesis in transcription - initiates TS at DNA sequences corresponding to the 5' cap of mRNA

Promoter

specific region of a gene where RNA polymerase can bind and begin transcription