Regulatory gene expression

transcriptional control

2nd main level for controlling gene expression

differential gene transcription result

different proteins produced by 2 cell types in the same individual result

transcription factors

proteins that determine specificity of transcription

general transcription factors

essential for transcription of all genes transcribed by a given type of RNA polymerase

where do general transcription factors assemble with RNA polymerase

at the core promoter very close to the transcription startpoint

what is common with each gene

CAAT box, GC box, octamer (ATGCAAAT)

regulatory transcriptions factors

transcription factors that bind one either CAAT box/GC box/octamer 

enhancers

stimulate gene transcription

silencers

inhibit transcription

transcriptional activators

regulatory factors that bind enhancers

coactivators

include chromatin-remodeling proteins and enzymes tat modify histones

mediator

multiprotein complex that acts as a bridge that binds to activator proteins associated with enhancers and to RNA polymerase

combinatorial

multiple control elements and transcription factors act in combinations to establish patterns of gene expression in different cell types

how do regulatory transcription factors bind to specific DNA sequence

DNA-binding domain

how do regulatory transcription factors regulate transcription

activation domain

recognition helix

binds DNA and second helix stabilizes the overall configuration

zinc finger

motif that consists of an alpha helix and 2-segment beta sheet held in place by hte interaction of cysteine and histidine residues with a zinc ion

protrudes from protein surface and act as points of contact between protein and DNA

helix-loop-helix motifs

contain short alpha helix connected by a loop to another longer alpha helix

contain hydrophobic regions that usually connect 2 polypeptides either similar or different

leucine zipper motif 

formed by interaction between 2 polypeptide chains each with regularly spaced leucine residues

leucine interact with one another and interlock causing 2 helices to wrap around each other

homeotic genes

an unusual class of genes that when mutated cause transformation of one body structure into another

alternative splicing

permits some splice sites to be skipped and others activated to create different mRNAs from the same pre-mRNA

what do regulatory proteins bind to sequences in pre-mRNA

splicing enhancer or splicing silencer

splicing enchancers

SR proteins

splicing silencer

heterogeneous nuclear ribonucleoprotein, hnRNPs

heme-controlled inhibitor (HCI)

protein kinase that is inactive in presence of heme

in absence of heme, HCL phosphorylates and inhibits elF2. a protein required for initiating translation

elF4F

multiprotein complex that binds 5’ mRNA cap regulated by phosphorylation

adenovirus

inhibits proteins synthesis in infected cells by blocking phosphorylation of elF4F that is normally required for its activation

3’ to 5’ mRNA degradation pathway

shortening of the poly(A) tail → exosome degradation of the RNA chain with 5’ cap degraded last

5’ to 3’ mRNA degradation pathway

shortening the tail at the 3’ end → removal of cap → degradation of mRNA by mRNA processing bodies (P bodies)

RNAi (RNA interference)

double-stranded RNAs from certain types of viruses of introduced artificially are cleaved by cytoplasmic ribonuclease (dicer) into short fragments ~21-22 bp long (siRNAs/small interfering or silencing RNAs) 

RISC (RNA-induced silencing complex)

an inhibitor of gene expression formed by siRNAs combining iwth a group of proteins

when siRISC is guided to a target mRNA and if a base pairing is extensive…

mRNA is degraded by an Argonaute protein

when siRISC is guided to a target mRNA and if pairing is not extensive…

mRNA stability and/or translation of message is inhibited

siRISC may also enter nucleus and be guided to DNA complementary to siRNA

may silence expression of sequences through DNA methylation and/or recruiting proteins that methylate histones

microRNAs (miRNAs)

produced by genes found in almost all eukaryotes

primary microRNAs (pri-miRNAs)

miRNAs that are initially transcribed into longer molecules folding into hairpin loops

drosha

converts looped pri-miRNAs into mature miRNAs in the nucleus with associated proteins

dicer

converts looped pri-miRNAs into mature miRNAs in the cytoplasm with associated proteins

posttranslational control mechanisms

structural alterations that influence protein function, protein folding guide, target specific locations, interactions with regulatory molecules

ubiquitin

small protein containing 76 amino acids

components of ubiquitin in target proteins

ubiquitin-activating enzyme (E1), ubiquitin-conjugdating enzyme (E2), substrate recognition protein or ubiquitin ligase (E3)

proteasomes

large protein-degrading structures and prodominant proteases of the cytosol, binds ubiquitin-labeled proteins and remove the ubiquitin

fed into central channel of proteasome and peptide bonds are hydrolyzed in an ATP-dependent manner