GENES AND VARIATION OBJECTIVES: 16.1 Explain what a gene pool is.
Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5
description
Transcript of Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5
![Page 1: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/1.jpg)
Regulation of Gene ExpressionCh. 16.1-16.2;16.4-16.5
![Page 2: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/2.jpg)
1 Embryo 200 Cell Types• From a single embryo, 200 types of
cells can be produced (differentiation)
• Diversity comes from genes being turned off
• Expression of the genes lead to specialization of the cell
• Transcriptional regulation controlling the expression of genes
1) post-transcriptional effect mRNA
2) Translational protein translation3) Post-translational life
span/activity of protein
![Page 3: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/3.jpg)
Regulation in Prokaryotes• Adjust biochemistry quickly
as environment changes• Jacob and Monod
extensive studies into the effects of lactose on expression of lactase genes
• Operon regulatory sequence in DNA for a specific gene(s) + the genes
• Regulatory proteins bind to operons to promote or inhibit the transcription of transcription unit (single mRNA coded in the operon)
![Page 4: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/4.jpg)
Regulation of an Operon• Operator section at the
start of the operon• Activator protein
attaches to operator to promote expression
• Repressor protein attaches to operator to inhibit expression
• Gene coding for regulatory proteins (activators/repressors) are called regulatory genes
• Non-regulating proteins come from structural genes
![Page 5: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/5.jpg)
The lac Operon• 3 genes:1) lacZ codes for β-galactosidase;
breaks lactose into glucose + glactose
2) lacY codes for permease; actively transports lactose into the cell
3) lacA codes for transacetylase; We don’t know what it does
• Negatively regulated– Regulator gene lacI codes for Lac
repressor– Limits lac expression when lactose is
absent (normal)– When lactose is added, it is made into
allolactose (inducer for lac operon) – Inhibits lac repressor by binding to it
![Page 6: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/6.jpg)
Lac Operon Part II; Positive Regulation• Lac operon is repressed in the
presence of lactose if glucose is also added. Why?– Glucose is a better source of energy– Converting lactose into usable
sugars (glucose) requires energy• CAP (catabolite activator protein)
activator synthesized in an inactive form; activated by cAMP (produced when glucose is absent)– Active form binds to CAP site at the
lac operon promoter allowing RNA Poly to attach
• If we add glucose, cAMP levels drop so CAP is deactivated and RNA Poly can bind to the DNA
![Page 7: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/7.jpg)
trp Operon and Protein Synthesis• Some proteins, like
tryptophan, must be synthesized when not present to be absorbed
• trp Operon codes enzymes needed to make tryptophan; regulated by trpR (repressor) that is normally inactive; trp operon used to make tryptophan
• When tryptophan levels are high, the repressor is active and trp operon is blocked (repressible operon)
• Tryptophan is a corepressor; activates repressor
![Page 8: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/8.jpg)
Regulation in Eukaryotes• Eukaryotes do not have
operons; regulatory gene are spread across the genome (side effect of variation)
• Eukaryotes use all forms of gene regulation:
1) Transcriptional Regulation2) Post-transcriptional
regulation3) Translational regulation4) Post-translational
regulation
![Page 9: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/9.jpg)
Transcriptional Regulation• Promoter region of DNA
upstream (~25bp) from the transcription unit– TATA Box 7-bp sequence
5’-TATAAAA-3’• TFs (transcription factors)
recognize TATA and bind to it; then RNA Poly II can bind
• Further upstream are the regulator sequences (promoter proximal elements) in the promoter proximal region
• Regulatory proteins bind here to enhance or repress transcription
![Page 10: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/10.jpg)
Activators and Transcription• RNA Poly II + TFs transcription
initiation complex; not that efficient
• Activators proteins that help the complex attach and start translation
• Activators can be specific (one cell type for one gene) or general (multiple genes in all cell types) which are also called Housekeeping genes
• Enhancer regions on the DNA can increase transcription rate by interacting with activators (act as coactivators) by bending DNA into a loop
![Page 11: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/11.jpg)
Motifs in DNA Binding Proteins• Domains structures in a protein made
from the combination of secondary folding options (helix, sheet, coil)– Ex. Helix-helix-coil-helix
• Motif specialized domains conserved in different types of proteins
• DNA interacting Motifs:1) Helix-turn-helix DNA binding region
of protein2) Zinc Finger finger shape with zinc
ion; bind to DNA grooves3) Leucine zipper dimers held together
by hydrophobic regions; bind to major groove of DNA
![Page 12: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/12.jpg)
Combinational Gene Regulation• Regulation of most genes in more
complex than just activation or repression
• Genes can have multiple activators and repressors
• These regulation points between different genes overlap and follow the stronger influence
• Gene A is regulated by enhancer regions 1, 2 and 3; Gene B is regulated by enhancer 2, 3, and 4– Activators on 2 and 3 will produce A
and B proteins – Repressors on 3, and 4 will limit B
protein a great deal and A proteins a little bit
![Page 13: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/13.jpg)
Coordinated Regulation• Proteins can be regulated
in complex organisms across many types of tissues through chemical signals (hormones)
• Steroid Hormone Response Element region in gene that hormone-receptor complex binds to– Allows regulation in
several cell types very quickly
![Page 14: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/14.jpg)
Methylation of DNA• DNA methylation adding methyl
(-CH3) to cytosine bases– Turn off gene (silencing) by
blocking access to promoter region• Epigenetics change in gene
expression but no change in the DNA itself
• Hemoglobin turned off in all other cell types this way
• Genomic Imprinting silencing of one of two alleles during development– Methylated allele is not expressed
![Page 15: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/15.jpg)
Chromatin Structure• Histones can block access
to DNA and thus regulate it• Chromatin remodeling
changing its structure– Nucleosome remodeling
complex moves histones along DNA or reshapes them to open a region
• Adding Acetyl Groups (CH3CO-) weakens the interactions between the histones and DNA
• Methylation of Histones marks histones wrapped with deactivated DNA
![Page 16: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/16.jpg)
Gene Regulation in Development• Gene regulation is most
important during early development; determine the cell-types and physiology of the organism
• Regulation sensitive to both time (must all happen in the right order and within a certain window) and place (location in embryo determines location in body)
• Understanding comes from our model organisms:– Fruit fly, nematode worm,
zebrafish, and house mouse
![Page 17: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/17.jpg)
From Zygote to Fetus• After fertilization, a zygote
develops into a fetus through several mechanisms
1) Mitosis need lots of cells2) Movement of cells cells need to
form the right shape3) Induction cell of a certain type
needs neighboring cells to respond to get a result
4) Determination totipotent cells becomes specific cell types
5) Differentiation cell types become finalized so tissue and systems can be made
![Page 18: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/18.jpg)
Hold Up Mr. Nucleus…Cytoplasm has something to say…
• Not all regulation of a zygote comes from the nucleus
• Zygote’s cytoplasm is from the egg used at fertilization
• Cytoplasmic determinants– mRNA strands and proteins in cytoplasm
of egg also regulate the zygote– Not reproduced during cell divisions;
First divisions of zygote separate determinants asymmetrically so each daughter as an uncontrolled amount
– Only really take effect during the first few divisions but can last till tissues form
– Inherited only on the maternal side
![Page 19: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/19.jpg)
Induction• Major step in the process of
determination• Signal molecules from very
specific cells (inducers) sent to receptor cells
• Two methods:1) Signal released and travels
short distances to receptors
2) Cell-to-Cell contact between proteins in the membranes of inducers and receptors
![Page 20: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/20.jpg)
Differentiation• Determination narrows the
type of cells possible and differentiation limits to one cell type
• Genes required for cell type are left on while other genes are “turned off”
• Master regulatory genes promote the transcription of proteins needed to specialize the cell– myoD master gene regulates
MyoD transcription factors which promotes skeletal muscle proteins
![Page 21: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/21.jpg)
Physical Position and Regulation• Pattern formation
arrangement of organs in the body– Discovered studying the
effects of mutations on the embryogenesis of fruit flies
– Particular genes control the body plan for all complex organism
• Steps required:1) Determine front, back,
head, and tail (ventral, dorsal, anterior, and posterior) of embryo
2) Divided zygote into segments
3) Use segments to map out body plan
![Page 22: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/22.jpg)
Maternal-Effect Genes• Expressed when egg is
produced by the mother; mRNAs made from the bicoid gene
• Control the anterior-to-posterior polarity of the egg (front to back)
• Bicoid protein is produced and the highest conc. marks the anterior (head) and drops as move along to the posterior (butt) which has the lowest conc.
![Page 23: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/23.jpg)
Segmentation Genes• 24 genes divide embryo
into regions• 3 Types:1) Gap Genes form
segments along A-P axis; broad regions
2) Pair-rule Genes divide broad regions with units of two segments each
3) Segment polarity Genes sets the boundaries for each segment; each segments needs an A-P axis
![Page 24: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/24.jpg)
Homeotic Genes• Genes specify which
segment becomes what; where are the legs, eyes, wings, etc…– Hox genes– 8 Hox genes in fruit flies– Actually occur in order on
chromosome (AP)– Found in all animals and is
highly conserved• Homeo-Box region in all
homeotic genes that codes for its specific homeodomain (TF for its protein)
![Page 25: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/25.jpg)
Genes and Cancer• 2 types of Cancer1) Familial Cancer inherited; common
with breast, colon, and testicular cancers
2) Sporadic Cancer occur randomly; more common form; can happen from viruses altering DNA
• All cancer is a multi-step process; need several key mutations
• 3 Classes of Genes effect cancer frequency:
1) Proto-oncogens2) Tumor suppressor genes3) microRNA genes
– (not covering this)
![Page 26: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/26.jpg)
Proto-Oncogenes• Genes that stimulate cell division
in regular healthy cells• Code for growth factors, signal
receptors, transduction components, and TFs
• When mutated, they can become overactive oncogens
• Only one allele needs mutated to take effect– Mutation in the promoter – Mutation in the transcription unit– Translocation moves gene to a
more active promoter or enhancer– Virus adds genes that activate or
enhance a gene
![Page 27: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/27.jpg)
Tumor Suppressor Genes• Code for proteins that inhibit
cell division• Keep Proto-oncogenes
repressed• TP53 codes for p53 that
inhibits CDKs used to pass the G1/S checkpoint
• If mutated, p53 can’t inhibit division
• p53 mutations are in 50% of all cancers
• Both alleles must be inactive for a tumor suppressor gene to lose function
![Page 28: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/28.jpg)
Homework• Suggested Homework:– Test Your Knowledge Ch.
16• Actual Homework:– Discuss the Concepts #1– Interpret the Data Ch.
16– Design the Experiment
Ch. 16
![Page 29: Regulation of Gene Expression Ch. 16.1-16.2;16.4-16.5](https://reader035.fdocuments.in/reader035/viewer/2022062501/568166da550346895ddafb6b/html5/thumbnails/29.jpg)
Assignments for Next Week• PPT Presentations on Ch. 18:
– Groups of 3; 12-15 mins long– Topics:
• DNA Cloning and Building DNA Libraries• Gel Electrophoresis, Southern Blot, Northern Blot, and Western Blot• DNA Cloning and Bacteria Transformation for Protein Synthesis• BLAST Program and How it is Used
• Papers on Ch. 19:– 3 page paper discussing the following:
• Darwin’s Journey• Data and Experiments by Darwin• World Reaction to Darwin’s Theories• Basic Principles of Evolution
– DO NOT answer these section by section. These are the BIG IDEAS you paper must discuss. It should be a summary of Darwin’s life and impact on Biology