Ch18 Gene Expression PPT Notes

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Gene Organization and

Expression
Review
 How many chromosomes? multiple

 Shape of chromosomes? linear

 Nucleus in euks isn’t only place to find DNA

 mitochondrial DNA, chloroplast DNA


Prokaryotic gene organization
 Multiple
genes for a single metabolic
pathway all accessed through single
promoter

 Promoter + multiple genes = operon


Regulating gene expression
 Organisms don’t make proteins that are not
needed (recall energy expense)
 Feedback inhibition
 Environmental signals can turn genes “on”
and “off” by modifying access to promoter;
repress transcription
 Operon Model
1) Inducible operons
2) Repressable operons
Inducible operons: positive control
 Idea: keep genes “off” normally unless
substrate is available for enzymes to use

 Ex: lac operon,


blocked promoter
and “off” b/c no
lactose is present
Inducible operons
 When lactose available, it binds to repressor
and causes it to fall off promoter and genes
turn “on” that can code for lactase.
Repressible operons: negative control
 Idea: keep genes “on” until enough product
is made by the enzymes they code for
 trp operon: default is active, enzymes

produced to make tryptophan amino acid


Repressible operons
 trp operon: if lots of tryptophan, it binds to
regulatory molecule that blocks promoter
Summary

 inducible operon – keep “off” until substrate


is available to turn genes “on”

 repressible operon – keep “on” to make more


enzymes and/or product until enough
product turns “off”
 https://www.khanacademy.org/science/ap-biology/gene-ex
pression-and-regulation/regulation-of-gene-expression-an
d-cell-specialization/v/dna-and-chromatin-regulation
Human genome
Need for Regulation
 Expensive endergonic energy process
Differential gene expression

 Cell’s task is to find and activate the right


gene at the right time
 Cells turn genes “off” and “on” in response to

internal or external environmental changes


 Cells need to regulate gene expression

during development (ch 21p. 457-458): hox


& hedgehog genes)
Organizational system
 more DNA than proks, eukaryotes need packing
system: Histone + DNA = nucleosome
◦ + a.a.’s are attracted to – phosphate backbone
 Use histone proteins to pack / unpack regions
◦ Heterochromatin/euchromatin
Regulating transcription:
1. Histone packing
Two regulatory systems in eukaryotes:
1) Histone packing / unpacking DNA regions
H.chromatin too tightly packed = blocking RNA
poly. access=no transcription
Eu.chromatin loosely packed = can be transcribed

2) Transcription factors regulating RNA


polymerase access to promoter
(like prokaryotes)
Histones and regulation con’t.
 Enzymes add chemical groups to histones to
change DNA packing
 Acetylation – loosens DNA by adding - acetyl

grps to + lysines in histone tail; neutralizes


charge and loosens packing
(more transcription due to access to promoter)
 Methylation – packs DNA tightly; represses
transcription
(less transcription due to less access to promotor)
Genes are more heavily methylated in cells
where they are/are not expressed.
Histones and DNA packing

methylated
histones
(or DNA) =

more packing =

less transcription

acetylated histones

less packing =

more transcription
Why modify gene expression?
Environmental signals cause changes in expression –
signal transduction and the “nuclear response”
2. Transcription factor regulation

promoter regions
(similar to proks)
Euk regulation complex –
multiple protein interactions
Transcription factors
regulate RNA poly access to
promoter

Can turn expression


“on / off” and “up / down”
Transcription Control summary (now would be a good
time to review vocab)
 1)chromatin modifying enzymes initial control by

making a gene region of DNA more or less


accessible.
 2) modifying pre-mRNA

 3) control elements: seg of non coding DNA that

bind to proteins to regulate expression


 4) transcription factors: proteins that assist RNA

polymerase
◦ a. enhancers b. activators c. repressors

What was the ultimate goal of gene


regulation?
Stem cell basics
 Generally, stem cells undergo mitosis, then
new cells differentiate

 Different types of stem cells

totipotent  pluripotent  multipotent 

?
(embryonic) (somatic:ex. bone
marrow)
Umbilical cord blood stem cells: somewhere in
between
Stem cells: differentiation
 Cell differentiation - becoming a certain
type of cell by activating certain genes
 https://learn.genetics.utah.edu/content/stemcells/scintro
Epigenetics and stem cells
 Cell differentiation - becoming a certain type
of cell by activating certain genes
 Guess the Embryo (wgbh.org)
Gene – environment interaction
 Studied in a field called epigenetics:

 How does a cell change its gene expression


profile in different environments?

 What controls phenotypic expression of


genotype?

Genes AND environment:


https://learn.genetics.utah.edu/content/epigenetics/rats
Cancer: Malfunctioning Cell Cycle
Control…review from last semester
 Mutations that alter genes that control:
(ch. 12) mitosis, growth factors (density
dependent inhibition), receptors, cell signaling
molecules(MPF, cdK’s, M phase checkpoint,
tumor-suppressor genes, etc)

Some viruses linked to cancer: epstein-barr,


herpes, HPV, some leukemia’s and
lymphoma’s)
“cancer genes”
 How might a proto-oncogene that once
functioned normally begin to malfunction and
become an oncogene?

◦ Movement of DNA w/in genome


By translocation
By transposons and retro-transposons
◦ Point mutations
◦ Amplification
“cancer genes”
 ras gene (proto-oncogene)
problem with cell signaling cascade
Mutation causes hyperactive ras protein to trigger
kinase cascade prematurely.
What is the effect of this?

 p53 gene (tumor suppressor gene)


o halts cell cycle for DNA repair
o activates genes that can repair DNA
o activates genes that trigger apoptosis

 Telomerase prevents natural shortening of


telomeres
Post Transcriptional Control
RNAi – RNA interference
 miRNA = microRNAs

 Can bind to mRNA sequence and block


translation
Transposable Elements and
Repetitive DNA
 Transposons: Segments of DNA that move
locations with in genome using a “cut and
paste” method or “copy and paste” method

 Retrotransposons: move locations using RNA

 Rep DNA: mistakes in replication or


recombination
 Simple seq DNA: tandem repeats located

telomeres and centromeres, role in chrom


structure, organize chromatin interphase
Gene families and pseudogenes
Pseudogene – similar to other active gene, either
never transcribed or not translated anymore

Human genome has many pseudogenes


Gene duplication
Unequal crossover
can occur to give
2 copies of an
allele on one
chromosome

Useful for evolution –


mutation modifies
one gene while other
still makes needed
protein

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