Transcript Genetics of Viruses and Bacteria

Chapter 18- Regulation of
gene expression
• You Must Know
o
o
o
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Functions of 3 parts of an operon
Role of repressor genes on the operon
Impact of DNA methylation and histone acetylation on gene expression
Role of oncogenes, proto-oncogenes, and tumor suppressor genes
Bacteria Response to
Environmental Change
• Regulate Transcription
• Bacteria are favored by
Natural Selection
o Reproduces quickly
o Produce what it needs
o Regulates enzymatic production
by feedback inhibition or gene
regulation
o Gene expression by the operon
model
Bacteria (prokaryotes)
• Anatomy of a Bacteria
o Peptidoglycan-found in cell
wall
o Membrane, cell wall
o Binary fission
• Reproduce @ 20 minutes
o Conjugation
• Exchange of genetic material
and information
• F plasmid, F+ donates to F• R plasmids- resistance
Environmental Impacts
on Bacteria
• In our “gut”bacteria must
respond to what we eat
• Lacks tryptophan (aa in
turkey that makes you
sleepy) bacteria actives
another pathwayfeedback mechanism
• You pig out on turkey,
bacteria will stop
manufacturing
tryptophan- feedback
inhibition
Bacteria in Colon
• Respond to what the host eats
• Sounds like + and – feedback
• Low tryptophan, must
manufacture
• High Tryptophan
o Stop
Bacterial Genes
• Clustered into units
called OPERONS
• 3 parts
o Operator
• Controls RNA polymerase
access to genes
o Promoter
• Where RNA polymerase
attaches
o Genes of the operon
• DNA required for all enzymes
produced buy the operon
Operator
• On switch for segment of
DNA
• Positioned in promoter or
between the promoter
and enzyme coding genes
• Controls access point of
RNA polymerase
• Operator, promoter and
genes they control is
operon
Promoter
• Point of attachment for
RNA polymerase
Genes of the Operon
• Entire stretch of DNA
o Codes for all enzymes produced by
the operon
Regulatory Proteins
• Produce Repressor
Proteins
• Located some distance
from the operon
• bind to the operator site
• When binding Blocks
RNA polymerase
o Operon is off
o Corepressor can bind to the
repressor protein and activate it
Repressor
• Is the protein OFF switch
• Prevents gene
transcription
o
o
o
o
o
Binds to the operator
Blocks RNA polymerase
Part of a separate regulatory gene
Can be active or not
Corepressor molecule works with
repressor protein to switch off the
operon
Bozeman
• Lac Operon
• Remember PROG
o Promoter
o Repressor
o Operator
o Genes
2 Types of Operons
Repressible
• Tryp Operon-Normally
on
o Can be inhibited
o Anabolic for building organic
molecules
o repressor protein is inactive.
o Produced molecule can act as
a corepressor and binds to the
repressor protein and actives
it
o Binds to the operator site and
shuts down the operator
Inducible
• Lac Operon
• Normally off
o Can be activated
o Catabolic-breaking down
macromolecules
o Repressor protein is active
o small molecule called
inducer binds to and
inactivates the repressor
o Repressor out of the
operator site, RNA
polymerase can access the
genes of the operon
Inducible Operon(enzymes)
Normally off but can be activated
• Catabolic, breaking down food
• Repressor protein is active
• To turn ON Inducer binds to
and inactivates the repressor
protein
• RNA poly can access genes of
the operon
Inducible Operon
Repressible
• On all the time, can be
turned off
• Anabolic
• Synthesize essential end
products from raw materials
• Suspend production of end
product when it’s present
conserves resources
Repressible Operon
Remember
• Bacterial DNA
• a circular chromosome
plus plasmids. The DNA of
most bacteria is
contained in a single
circular molecule, called
the bacterial
chromosome. The
chromosome, along with
several proteins and RNA
molecules, forms an
irregularly shaped
structure called the
nucleoid
Eukaryotic gene
Expression
• Regulated at any stage
• Can be turned on/off
at any point along the
pathway from geneprotein
• Differences of cell
types is not due to
different genes, but
differential gen
expression
Eukaryotic Gene Expression
Regulated at many stages
Regulation of Chromatin
Structure
• Fundamental Packaging of
DNA
• Nucleosome
o DNA bound to small
histone proteins
o More tightly bound, less
accessible for
transcription
Regulation of Chromatin
Structure
• DNA binding to
histones
• Dependent on 2 things
o DNA Methylation
o Histone acetylation
Chromatin Structure
• DNA Methylation
o Add methyl groups to
DNA
o Becomes tightly packed
o Reduces gene
expression
o Cannot transcribe or
translate
Chromatin Structure
• Histone Acetylation
o Acetyl groups added to the
amino acids of histone protein
o Less chromatin binding
o Encourages transcription
Transcriptional
Regulation
o Transcription
Initiation Complex
• Enhances gene expression
o DNA control elements bind
transcription factors to initiate
transcription are involved in
regulation
o DNA sequences far from the
gene called enhancer regions
are bound to the promotor
called activators=
Post-Transcriptional
Regulation
• RNA processing
o Poly A tail, 5’cap, RNA splicing
and transcript
• mRNA Degradation
o Nucleotide sequence in
nontranslated region (UTR)
o Relative short life span mRNA
• Initiation of Translation
o Poly A tails, 5’tails
• Protein
Processing/Degradatio
n
o Proteasomes mark protein for
destruction with ubiquitin
Noncoding RNAs play a roles in
gene expression
• Prior to translation
• After translation
• Impacts on mRNA by
MicroRNA and Small
Interfering RNA
• Noncoding RNAs play
a role
o Small, single strand RNA can
complex with protein and
influence expression
RNA ProcessingTypes
• Impact gene
expression
• MicroRNA (miRNA)
o Bind to mRNA
o Degrade mRNA
RNA Types
• Small interfering RNAsiRNA
o Bind
o Degrade
o Block translation
Chromatin Remodeling
by ncRNA
• Class called piwi
associated RNA, piRNA
o Induce heterochromatin
formation that blocks
expression of some parasitic
DNA elements called
transposons
Differential Gene Expression in
Multicellular Organisms
• Multicellular organism
• Zygote undergoes
transformation 3 ways
o 1. Cell division
• Increases number of cells
o 2. cell differentiation
• Cells specialize
o 3. Morphogenesis
• Organization of cells into
tissues and orgns
Controls of Differentiation
and Morphogenesis
• Cytoplasmic
determinants
o Maternal substances in the egg
o Influence the course of
development
o Distributed unevenly in cells of
embryo-different affects
Controls
• Cell to cell signals
o From molecules
• Growth factors produced
by one cell influencing
neighboring cells called
induction
• Causes differentiation
Controls
• Determination
o Observable differentiation
o Irreversable
• Pattern formation
o Head, tail, back, front
o Body plan based on
cytoplasmic determinants
o Inductive signals
Cancer
• Cell cycle
controlchanges
• Oncogenes
o Cancer causing genes
o Proto-oncogenes
• Genes that code for
proteins for normal cell
growth
• Proto-oncogenes transform
with a mutation to become
oncogenes and increase
the activity of the protein
Cancer
• Tumor suppressor Genes
• Normal gene whose
products inhibit cell division
o P53 gene halts
cancer 3 ways
• 1. halts the cell cycle
• 2. turns on genes for DNA
repair
• 3. If too much damage,
activates suicide genes for
APOPTOSIS
Cancer Development
• Cancer is an
accumulation of
mutations throughout
life
• Longer we live greater
accumulations
• Greater chance for
cancer
BRCA-1 and 2
• Tumor suppressor genes
o Blood test to check for mutation
o the long (q) arm of chromosome 17 at
position 21.
o BRCA-2- chromosome 13
Chapter 18 Summary
Level of Control
Examples
Chromatin modification
DNA packing into nucleosome,
methylation(DNA-decreases
transcription,, acetylation added to aa
of histones-increases, ncRNA
heterochromatin
Transcriptional Regulation
Transcription factors/activators bind
control elements to form
transcriptioncontrol elements,s
repressors inhibit
RNA processing
RNA splicing, 5’ cap, poly A tail
RNA degradation
miRNA, siRNA, short life span mRNA
Translation regulation
Repressor, miRNA, siRNA prevent
translation, activation initiator factors
Protein processing/degradation
Cleavage, selective degradation by
proteosomes marked with ubiquitin
Regulation of Gene
Expression
Differential Gene
Expression
1. Cell division
Increases the number of cells
2. Cell
differentiation
Cellular specialization
Cytoplasmic determinants in the egg influence development
Cellular signaling uses molecules such as growth factors are
produced by one cell and influence neighboring cells and stimulate
induction (differentiation)
Determination- observable differentiation of a cell
Pattern formation-is result of cytoplasmic determinants for
the body plan of an organism
Morphogens- substance unevenly distributed establishes
axes
Homeotic Genes-control pattern formation
3.Morphogenesis
Shape of an organism
Same as differentiation