Chapter 7 – Linkage, Recombination, and Eukaryotic Gene Mapping
GENE REGULATION RESULTS IN DIFFERENTIAL GENE EXPRESSION, LEADING TO CELL SPECIALIZATION Eukaryotic...
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Transcript of GENE REGULATION RESULTS IN DIFFERENTIAL GENE EXPRESSION, LEADING TO CELL SPECIALIZATION Eukaryotic...
Gene Regulation results in differential Gene Expression, leading to cell Specialization
Eukaryotic DNA
Epigenetics – TED Talk
Watch to see how your environment and your choices influence inheritance…
http://youtu.be/JTBg6hqeuTg
Differential Gene Expression Nucleosome Packing: DNA wraps around histone proteins to form a structure called a nucleosome. Nucleosomes help pack DNA into eukaryotic chromosomes. When acetyl groups attach to the histone proteins the DNA in chromosomes loosens to allow for transcription.
The addition of methyl groups to histone proteins can cause DNA to condense thus preventing transcription.
In Genomic Imprinting, methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development.
Fig. 18-8-3
Enhancer(distal control
elements)
Proximalcontrol elements
Poly-A signal
sequenceTermination
region
DownstreamPromoter
UpstreamDNA
ExonExon ExonIntron
Intron
Exon Exon ExonIntron
Intron Cleaved 3
endof primarytranscript
Primary RNA
transcript
Poly-A
signal
Transcription
5
RNA processingIntron
RNA
Coding segmentmRNA
5 Cap 5 UTRStartcodon
Stopcodon 3 UTR Poly-
Atail
3
Organization of Typical Eukaryotic Genes
The Roles of Transcription Factors
To initiate transcription, eukaryotic RNA polymerase requires the assistance of proteins called transcription factors
General transcription factors are essential for the transcription of all protein-coding genes
In eukaryotes, high levels of transcription of particular genes depend on control elements interacting with specific transcription factors
An activator is a protein that binds to an enhancer and stimulates transcription of a gene
Activators have two domains, one that binds DNA and a second that activates transcription
Bound activators facilitate a sequence of protein-protein interactions that result in transcription of a given gene
Some transcription factors function as repressors, inhibiting expression of a particular gene by a variety of methods
Some activators and repressors act indirectly by influencing chromatin structure to promote or silence transcription
The Roles of Transcription Factors RNA polymerase requires the assistance of transcription factors in order to transcribe DNA into RNA.
Regulatory Proteins, repressors and activators, operate similarly to those in prokaryotes, influencing how readily RNA polymerase will attach to a promoter region. In many cases, numerous activators are acting in concert to influence transcription.
Fig. 18-9-3
Enhancer TATAbox
Promoter
ActivatorsDNA
Gene
Distal control
element
Group ofmediator
proteins
DNA-bendingprotein
Generaltranscript
ionfactors
RNApolymerase
II
RNApolymerase
II
Transcriptioninitiation
complexRNA
synthesis
Coordinately controlled eukaryotic genes
A particular combination of control elements can activate transcription only when the appropriate activator proteins are present.
All cells of an organism have all chromosomes/genes but certain genes are only active in certain cells. The transcription factors present in the cell determine which genes will be active and which won’t (but they are both still present)
Fig. 18-10
Controlelement
s
Enhancer
Available
activators
Albumin gene
(b) Lens cell
Crystallin gene
expressed
Available
activators
LENS CELLNUCLEUS
LIVER CELLNUCLEUS
Crystallin gene
Promoter
(a) Liver cell
Crystallin gene
not expressed
Albumin gene
expressed
Albumin gene
not expressed
Post Transcriptional Regulation Alternate Gene Splicing - different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns
Fig. 18-11
or
RNA splicing
mRNA
PrimaryRNAtranscri
pt
Troponin T gene
Exons
DNA
Protein Processing and Degradation After translation, various types of protein
processing, including cleavage and the addition of chemical groups, are subject to control
Proteasomes are giant protein complexes that bind protein molecules and degrade them
Protein tobe degraded
Ubiquitin
Ubiquitinatedprotein
Proteasome
Protein enteringa proteasome
Proteasomeand ubiquitinto be recycled
Proteinfragments(peptides)
Ubiquintin tags proteins for degradation by proteasomes.
Noncoding RNAs role in gene expression
RNA Interference, noncoding RNAs play multiple roles in controlling gene expression. MicroRNAs (miRNAs) and Small inserting RNAs (siRNAs) are small single-stranded RNA molecules that can bind to mRNA. These can degrade mRNA or block its translation. The difference between the two is that they form from different RNA precursors.
Fig. 18-13
miRNA-proteincomplex(a) Primary miRNA
transcript
Translation blocked
Hydrogenbond
(b) Generation and function of miRNAs
Hairpin
miRNA
miRNA
Dicer
3
mRNA degraded
5
Cytoplasmic Determinants and Inductive Signals
An egg’s cytoplasm contains RNA, proteins, and other substances that are distributed unevenly in the unfertilized egg
Cytoplasmic determinants are maternal substances in the egg that influence early development
As the zygote divides by mitosis, cells contain different cytoplasmic determinants, which lead to different gene expression
Figure 18.17a(a) Cytoplasmic determinants in the egg
Unfertilized egg
Sperm
Fertilization
Zygote(fertilized egg)
Mitoticcell division
Two-celledembryo
Nucleus
Molecules of twodifferent cytoplasmicdeterminants
The other important source of developmental information is the environment around the cell, especially signals from nearby embryonic cells
In the process called induction, signal molecules from embryonic cells cause transcriptional changes in nearby target cells
Thus, interactions between cells induce differentiation of specialized cell types
Figure 18.17b (b) Induction by nearby cells
Early embryo(32 cells)
NUCLEUS
Signaltransductionpathway
Signalreceptor
Signalingmolecule(inducer)
Figure 18.20
Wild type Mutant
Eye
AntennaLeg
Homeotic genes control pattern formation in late embryo, larva, and adult stages; mutations in homeotic genes cause a misplacement of structures in an animal.
Tumor-Suppressor Genes
Tumor-suppressor genes help prevent uncontrolled cell growth
Mutations that decrease protein products of tumor-suppressor genes may contribute to cancer onset
Tumor-suppressor proteins
Repair damaged DNA
Control cell adhesion
Inhibit the cell cycle in the cell-signaling pathway
Suppression of the cell cycle can be important in the case of damage to a cell’s DNA; p53 prevents a cell from passing on mutations due to DNA damage
Mutations in the p53 gene prevent suppression of the cell cycle
Figure 18.24b
(b) Cell cycle–inhibiting pathway
Protein kinases
UVlight
DNA damagein genome
Activeformof p53
DNA
Protein thatinhibitsthe cell cycle
Defective or missingtranscription factor,
such asp53, cannot
activatetranscription.
MUTATION2
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