Gene Regulation results in differential Gene Expression, leading to cell Specialization

Eukaryotic DNA

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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

1

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