Unit 12
12.1 Overview of Gene Regulation
Gene regulation conserves energy
Bacteria regulate genes in response to charges in environment
E.coli carries genes that code for proteins that enables metabolization of lactose
B-galactosidase metabolizes lactose when E.coli is placed in an environment with lactose
Permease allows lactase to enter cell
Cell Differentiation
Cell differentiation is an example of gene regulation
Process by which cells become specialized into particular types with distinctive structure and functions
Gene regulation is responsible for producing different cell types
Gene regulation in developmental stages
Certain genes are expressed throughout developmental stages
different hormones are released during embryo stage, fetus stage, and from birth to adult
Gene Regulation occurs at different points
Bacterial gene regulation
Transcription: most common during transcription, regulates amount of mRNA made from genes
transcriptional regulation is an efficient way to regulate genes
Translation: can control ability of mRNA translated into protein
Post translation: protein amount or function may be regulated
Eukaryotic Gene expression
Transcription: common during transcription
RNA Modification: Eukaryotes modify mRNA transcripts differently than bacteria
Translation: another fairly common way of gene expression
12.2 Regulation of Transcription in Bacteria
Regulation of transcription involves regulatory transcription factors
proteins that bind to regulatory sequences rate of transcription
Repressors
binds to DNA and decrease the rate of transcription, known as negative control
Activators
increase rate of transcription, known as positive control
Operon
arrangement of 2 or more genes under a single promoter
lac operon in E.coli
Gene is an operon results in production of polycistronic RNA
mRNA that codes more than one polypeptide
12.3 Regulation of Transcription in Eukaryotes: Rules of Transcription Factor
Transcription regulation in eukaryotes have characteristics seen in bacteria
Combinatorial Control
many factors control expression of any given gene
Four steps
Activators stimulate ability of RNA polymerase to initiate transcription
repressors inhibit ability of transcriptions
Function of activators/repressors may be motivated in several ways
Activators are necessary to alter chromatin structure in region where gene is regulated
DNA methylation usually inhibits transcription
Eukaryotic Protein coding genes have a core promoter and regulatory elements
Core Product: TATA box and transcriptional start site form the core promoter
Transcriptional start site is the place in the DNA and where transcription actually begins
TATA box determines precise starting point for transcription
results in lowest level transcription known as basal transcription
Regulatory Elements: DNA segments that regulate eukaryotic genes
comes in two general steps
enhancers: play a role in RNA polymerase transcription
enhances rate of transcription
Silencers: prevents transcription of a given gene when expression isn’t needed
RNA polymerase II
There are three forms of RNA polymerase (I,II, and III)
Requires 5 different proteins to initiate transcription
known as general transcription factors (GTFs)
Preinitiation box: completed assembly of RNA polymerase II and GTFs at the TATA box
Activators and Repressors May Influence the functions of GTFs
Three steps to start of eukaryotic translation
activators bind to an enhancer
activator also interacts with coactivator
activator/coactivator complex improves ability of GTF
Function of TFIID is to promote the assembly of other GTFs
12.4 Regulation of Transcription in Eukaryotes
region of chromatin containing a gene may be in closed formation
makes transcription difficult to impossible
Open conformation is accessible to GTFs and RNA polymerase I
Transcription controlled by changes in chromatin structure
Chromatin remodeling complex: complexes of proteins that alter chromatin structure
uses ATP to drive a change
3 effects possible
It may bind to chromatin changing locations of nucleosomes
May evict histone octamer from DNA, creating gaps where nucleosomes aren’t found
May remove histone and replace it with variant histone
Histone Modifications Affect Gene Transcription
Histone acetyl transferase: an example of amino terminal tail undergoing modifications
Effects of covalent modifications of histones
may influence interactions between DNA and histone proteins
Provides binding sites that are recognized by other proteins
histone code hypothesis
Eukaryotic Genes are flanked by nucleosome free regions
Core promoter is found within nucleosome free region
Recruiting appears to be critical
activator binds to an enhancer in the NFR
activator then recruits chromatin-remodeling complexes and histone modifying complexes in the region
Actions of chromatin-remodeling complexes histone-modification
Histones are evicted, partially displaced, or destabilized so that RNA polymerase II can pass
DNA Methylation Inhibits Gene Transcription
DNA structure can be modified by covalent attachment of methyl groups
done via enzyme DNA methyltransferase
DNA methylation inhibits transcription in two ways
may prevent activator from binding to an enhancer
altering chromatin structure
Facultative Heterochromatin is a way to silence genes
Facultative heterochromatin: differs among different cells of body
thought to play a big role in silencing genes in a tissue specific manner
12.5 Regulation of RNA splicing and translation in eukaryotes
Alternative splicing: a form of regulation that allows an organism to use the same gene to make different proteins
This process is regulated
each cell type produces a unique set of splicing factors
Prevention of Ion Toxicity
Iron Regulatory Protein: RNA binding protein that controls mRNA that codes ferritin
Low Iron: IRP binds to regulatory element known as Iron regulatory element
High Iron: When ferritin is needed, Iron binds to IRP, causing a conformational change to IRE, causing ferritin to be released