Chapter 14

transcriptional-level control

the most efficient mechanism of gene regulation in bacteria

(IGF2) insulin-like growth factor 2

codes for a protein produced by both muscle and liver tissue, ie pigs that have more muscle and less fat

Prokaryotic vs Eukaryotic
(gene regulation)

prokaryots -> only transcriptional level

eukaryots -> transcriptional level dominates but other levels as well b/c they live longer and respond to many dif stimuli, also a single gene may be reglated in dif ways in dif types of cells

operon

gene complex consisting of a group of structural genes with related functions plus the closely linked DNA sequences responsible for controlling them

promoter

where RNA polymerase first binds to DNA before transcription begins, located the operon

operator

located on the operon, serves as the regulatory switch for transcriptional-level control of the operon

repressor protein

binds to the operator to prevent the RNA polymerase from attaching which keeps transcription from occuring

inducible operon

- normally turned off (ie lac operon)
- repressor protein is made in an active form hat bindsto the operator
- if lactose is present it i converted to allolactose the INDUCER which binds to the repressor protein and changes the repressor's shape
- the altered repressor cannot bind to the operator an the operon is transcribed

repressible operon

- normally turned on (ie trp operon)
- repressor protein made in an inactive form that cannot bind to the operator
- a metabolite (usually the end product of a metabolic pathway) acts as a COREPRESSOR
- when an intracellular corepressor levels are high, a corepressor molecule binds to the repressor, changing the repressor's shape so that it binds to the operato and thereby turns off transcription of the operon

Constitutive genes

neither inducible or repressible but active at all times

catabolite activator protein (CAP)

a regulatory protein that is produced constitutively, repressor proteins are too
- the activty of constitutive genes is controlled by how efficiently RNA polymerase binds to their promoter regions

negative control

- what repressible and inducible operons are under
- when the repressor protein binds to the operator, transcription of the operon is turned off

positive control

- what some inducible operons are also under
- an activator protein binds to the DNA and stimulates transcription of the gene
- CAP activates the lac operon, CAP binds to the promoter region which stimulates transcription by binding RNA polymerase tightly

cyclic AMP (cAMP)

- what CAP requires to bind to the lac operon
- levels of cAMP increase as levels of glucose decrease

posttranscriptional controls

- TRANSLATIONAL CONTROL: regulates the rate of translation of a particular mRNA
- includes FEEDBACK INHIBITION of key enzymes i some metabolic pathways

Regulation of Eukaryotic genes

-not normally organized into operons
- occurs at the levels of transcription, mRNA processing, translation, and modifications of the protein product

transcription initiation site

- needed for the transcription of a gene
- where transcription begins
- needs a promoter to which RNA polymerase binds
- in multicellular eukaryotes RNA polymerase binds to a promoter called a TATA BOX

upstream promote elements (UPEs) aka proximal control element

- the promoter of a regulated eukaryotic gene consists of an RNA polymerase-binding site and short DNA sequences known as UPEs
- the number and type of UPEs within the promoter region determine the efficiency of the promoter

enhancers

- located thousands of bases from the promoter
- control some eukaryotic genes
- help form an active transcription initiation complex
- specific regulatory proteins binds to enhancers and activate transcription by interacting with the proteins bound to the promoter

transcription factors

- DNA-binding protein regulators which control eukaryotic genes
- many are transcriptional activators, others are transcriptional repressors
- some have a helix-turn-helix arrangement and insert one of the helices into the DNA
- others have loops of amino acids held together by zinc ions
- some are LEUCINE ZIPPER PROTEINS that associate as dimers that insert into the DNA

domain

- each transcription factor has a DNA-binding domain

heterochromatin

densely packed regions of chromosomes which contain inactive genes

how are genes inactivate or activated?

- by changes in chromosome structure
- cells change chromatin structure from hetero' to eu' by modifying HISTONES (proteins that associate with DNA to from nucleosomes)

euchromatin

- loosely packed chromosome structure assaciated with active genes

DNA methylation

mechanism that perpetuates gene inactivation

Epigenetic inheritance

involves changes in how a gene is expressed

gene amplification

- some cells selectively amplify genes by DNA replication
- some genes whose products are required in large amounts exist as multiple copies in the chromosome

differential mRNA processing

- as a result, a single gene produces different forms of protein in different tissues
- such a gene contains a segment that can be either an intron or an exon
- intron --> sequence removed
- exon --> sequence retained

What do regulatory mechanisms do after mRNA is formed?

- increase the stability of mRNA
- allows more protein molecules to be synthesized before mRNA degredation

How does posttranslational control of eukaryotic genes occur?

- by feedback inhibition or by modification of the protein structure

How is a function of a protein changed?

- by KINASES adding phosphate groups
- by PHOSPHATASES removing phosphates

protein degradation

- proteins targeted for destruction are covalently bonded to UBIQUITIN
- a protein tagged by ubiquitin is targeted for degradation in a PROTEASOME (a large macromolecular structure that recognizes the ubiquitin tags)
- PROTEASES (protein-degrading enzymes) associated with proteasomes degrade the protein into short peptide fragments