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Gene Regulation
Process of controlling which genes in a cell’s DNA are expressed
Differential gene expression
Expression of different sets of genes by cells with the same genome
Differential gene expression allows different cells to
Carry out different functions
Trancsiption happens in the
Nucleus
Translation happens in the
Cytoplasm
Prokaryotic DNA is organized into a circular chromosome located in
Nucleoid region of cytoplasm
Genes with similar function or in the same biochemical pathway are organized in
Block called operons
Operons consist of
Promoter
Operator
Cluster of functionally related genes
Promoter
Nucleotide sequence within a gene that binds RNA polymerase to initiate transcription
Operator
Sequence of nucleotides near the start of an operon that acts as the key control “on-off” switch
Cluster of functionally related genes that are
Trancribed in a single mRNA strand containing multiple start & stop codons
Operons are regulated by
Repressors and activators
Repressors
Proteins that bind to operator to suppress transcription
Negative regulation
Proteins bind to the operator turning off expression
Activators
Protiens that bind to operator to activate transcription
Positive regulation
Positive regulation
Protein bind to operator turning on expression
Negative regulation by a repressor
The trp operon
trp operon controls genes needed for
Tryptophan biosynthesis
Tryptophan is scarce when
Repressor protein is inactive
Operon is on
Trptophan is plentiful when
Tryptophan molecules bind the repressor protein at the operator sequence
Operon is off
Tryptophan is a corepressor
Corepressor
Binds to and activates the repressor
Negative regulation example
Lac operon
In the absence of lactose
A repressor binds the operator blocking transcription
In the presence of lactose
Lactose binds to the repressor preventing it from binding the operator
Lactose acts as an
Inducer
Inducer
Inactivates the repressor and turns on transcription
Positive rehulation by an activator
Lac operon
In the absence of cyclic AMP
The catobolite activator protein does not bind which causes transcription to occur at a low rate
When glucose levels increase
cAMP binds to CAP protein complex
cAMP/CAP binds to a region near lac promoter
Increase transcription of genes needed to metabolize lactose
Eukaryotes do not have
Operons
Eukaryotic genes have more
complex regulation mechanisms
Gene regulation can occur at
Several different steps
Different steps of gene regulation
Chromatin modification
Transcription
mRNA processing
mRNA degradation
Translation
Protein processing
Protein Degradation
Chromatin modification deals with how
Chromosomes are packaged
Organization of chromatin
DNA is folded around histone proteins to create nucleosomes
In loosely packed euchromatin, nucleosomes control access of proteins to DNA
Genes with densely packed heterochromatin are usually not expressed
Epigenetic Regulation
Control of gene activity through modification to proteins and DNA that do not alter the nucleotide sequence but does alter gene expression
Epigenetic regulation condenses chromatin into
Hetero chromatin which reduces transcription
Epigenetic inheritance
Chemical modifications are passed on to daugher cells
Chemical modification of histones and DNA
Epigenetic regulation and inheritance
Regulation of transcription is the most common form of
Gene regulation in eukaryotes
Transcription factors
Proteins that help turn specific genes on or off by binding to DNA
Proteins bind to
specific DNA sequences
When proteins bind to specific DNA sequences what happens
They regulate the activity of RNA polymerase
Activators
Enhance or turn on a genes transcription
Repressors
Turn off gene transcription
RNA polymerase II requires
Transcription factors to initiate transcription
Some transcription factors bind to the
TATA box in the promoter
Some transcription factors bind to proteins including what
Other transcription factors and RNA polymerase II
Enhancer
DNA sequence that promotes transcription
What is each enhancer made of
Short DNA sequences called distal control elements
Activators bind to distal control elements and interact with
Transcription factors and other proteins
DNA bending protein changes
Shape of DNA and properly orients enhancer region
Post-transcription regulation allows a cell to
Rapidly fine-tune gene expression in response to environmental changes
Alternative RNA splicing
Different mRNA molecules are produced from the same primary transcript
mRNA degradation fine-tunes
Protein levels without altering transcriptions
mRNA degradation regulates how
Long transcripts are available for translation
RNA-Bidning proteins at the 5’ and 3’ untranslated regions influence the RNA
Stability
Regulation of translation
Translation can be blocked by regulatory proteins
Regulatory proteins bind to
Sequences of mRNA
After tanslation
Polypeptides undergo processing
The length of time each protein functions is
Regulated by selective degradation
Phosphorylation is used to
Activate protein
Genes associated with cancer are
Mutations that alter normal cell growth and division
Proto-oncogenes
Gene that regulate cell growth, division, and differentiation
Oncogene
A proto-oncogene that has mutated and drives uncontrolled cell division
Mutation in the what are common in human cancer?
Ras proto-oncogene
Tumor-supressor genes
Gene whose protein product inhibits cell division and prevents uncontrolled cell growth
Tumor suppressor gene p53
Mutated in over 50% of all cancer types
Proto-oncogene ras codes for
Ras protein that acts as a molecular switch in cell signaling pathways
Ras protein
G protein that relays a signal from a growth factor receptor on the cell surface to stimulate cell division
Mutation in the ras gene can lead to
Production of a huperactive Ras protein
The mutant oncogene produces a protein that
Does not require a growth factor to be activated
The p53 gene codes for transcription factor that
Sense DNA damage
When p53 is activated it
Halts the cell cycle to allow DNA repair
If damage is irrepairable
p53 triggers apoptosis
Multiple mutations are generally needed for
Full-fledged cancer
A cancerous cell is usually characterized by
At least one active oncogene and the mutation of several tumor-suppressor genes
Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes, leads to
Predisposition for cancer
During embryonic development
A fertilized egg gives rise to many different cell types
Differential gene expression leads to
Different cell types
Genes are regulated
Differently in each cell type
Cell differentiation
Process by which cells become specialized in structure and function
Cytoplasmic determinants are
Maternal substances in the egg that influence early development
An egg’s cytoplasm contains
RNA, proteins, and other substances that are unevenly distributed
As the zygote divides by mitosis
Cells contain different cytoplasmic determinants which leads to differential gene expression
Environment around the cell contribute to
Cell differentiation