14 Control of Gene Expression in Eukaryotes

8/13/2019 14 Control of Gene Expression in Eukaryotes

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CONTROL OF

GENE

EXPRESSIONEUKARYOTES

Chapter 19



Control of Gene Expression

Every cell has the same DNA

Cells are not identical… Why not?

Differences in Gene Expression

Only 5-10% of genes are expressedin a cell (eukaryotic) at any given time



Gene Expression

Gene Expression – process by which geneticinformation flows from genes to active proteins ;involves transcription and translation of a gene and

protein activation

Differences in gene expression

Differences in proteins that are active in a cell

Differences in cell characteristics



Importance of Regulating Gene ExpressionMulticellular Eukaryotes

Allows cells to respond to signals from other cells(changes in the internal environment)

Improves efficiency

Allows for cell differentiation during development



Cell Differentiation: Controlled byDifferential Gene Expression

http://mbscientific.com/wiki/Genetic_Machinery_of_Natural_Selection









Mechanisms of Eukaryotic GeneRegulation

Chromatin structure

TranscriptionalControl

Post-transcriptionalControl

(mRNA processing)

TranslationalControl

Post-translationalControl

Which of theseare unique toeukaryotes?

F a s t e r R e s p o n s e

M o r e E f f i c i e n t

mRNAStability




Chromatin Structure – condensed DNA is nottranscribed

Transcriptional Control – transcription factors regulategene transcription

Post-transcriptional (mRNAProcessing) Control – alternate splicing determinesprotein product




mRNA Stability – how fastmRNA is degraded affectsquantity of protein produced

Translational Control – initiation factors (interactingwith the 5’ cap) regulateinitiation of translation

Post-translational Control – polypeptide productundergoes modifications tobecome biologically functional



Structure of the EukaryoticChromosome

In a human cell:

2 m of DNA (3.2 billion base pairs)

5 µm nucleus

DNA must be highly compactedand organized!

There are several levels ofcompaction




Histones – proteinsresponsible for packaging DNA

Tight interactions exist betweenthe DNA(-) and histones (+)




Chromatin – material that makes up eukaryoticchromosomes; DNA-protein (histone) complex

Nucleosome – DNA wrapped nearly twice around a coreof 8 histone proteins



Hypothesis: due to tight packaging, RNA polymerasecannot access/transcribe genes; chromatin near

promoter must be remodeled in order fortranscription to begin

Chromatin StructureEffect on Gene Expression?



Chromatin RemodelingEffect on Gene Expression

Condensed chromatin(heterochromatin)

Open chromatin(euchromatin)

Gene NOT expressed“turned OFF”

Gene EXPRESSED“turned ON”

Example: Barr Bodies – condensed (inactive) X

chromosome in females



Chromatin RemodelingEffect on Gene Expression – Barr Bodies



Chromatin Remodeling Mechanisms

1. Chromatin remodelingcomplexes – utilize ATP toreshape chromatin



Chromatin RemodelingMechanisms

2. Acetylation and Methylation – add/remove acetyl (ormethyl) groups to histones/DNA using:

histone acetylase transferases (HAT’s) – decondense /“ON”

histone deacetylases (HDAC’s) – condense/“OFF”

Condensedchromatin

Decondensedchromatin

Acetylgroup onhistone



Chromatin StructureEpigenetic Inheritance

Epigenetic Inheritance – patterns of inheritance thatare not due to differences in gene sequences

Chromatin modifications (such as acetylation or methylation)can be passed from parent cell to daughter cells



Epigenetic Inheritance



Epigenetic Inheritance



Transcriptional ControlEukaryotic Gene Structure

Eukaryotic Gene – section of DNA that codes for one or morerelated polypeptides or RNA molecules along with the

promoter and regulatory sequences required for expression

Promoter – site in DNA where RNA polymerase binds to initiatetranscription; contains conserved sequences including TATA box



Transcriptional ControlRegulatory Sequences

Regulatory Sequences – sections of DNA involved in controllinggene transcription

Promoter-proximal elements –regulatory proteins bind to this site andenhance transcription (positive control)

Enhancers – when regulatory proteins bind to these sequences,transcription begins; may be located far from the promoter or even inintrons! (positive control)

Silencers – when regulatory proteins bind to these sequences,

transcription stops (negative control)



Transcriptional ControlRegulatory Proteins – Transcription Factors

Transcription of a eukaryotic gene is controlled by regulatory proteins known as transcription factors

Basal Transcription Factors – regulatory proteins (DNA-binding proteins) that bind to the promoter; required fortranscription initiation; common among all cell types

Regulatory Transcription Factors – regulatory proteins thatbind to promoter-proximal elements, enhancers, or silencers;responsible for expression of particular genes in particularcells at particular times; specific

Differential gene expression is the result of the production or

activation of specific transcription factors.



Transcriptional ControlRegulatory Proteins – Transcription Factors



Regulatory TranscriptionFactors (TFs)

Different cell types expressdifferent regulatory TFs

TFs are activated in responseto signals received by the cell

Regulatory Transcription Factors



Basal transcriptioncomplex:

TFs and RNA pol II



Regulation of Gene Expression… in Multicellular Eukaryotic Organisms

Extracellularsignals

Receptor protein in membrane

Intracellularsignals

RegulatoryProteins

(TranscriptionFactors)

1. Signal arrives at cell with message:“Become a muscle cell .”

Promoter

RNA polymeraseExon Intron Exon Intron Exon

TRANSCRIPTION

Gene for muscle-specific protein

EnhancerEnhancer

Cytoplasm

3. Transcription factors are producedor activated in response to

intracellular signal.

2. Signal transduction results in

production of intracellular signal.

4. Transcription factors bind to regulatorysites in DNA, triggering expression of cell-specific genes.



Transcription Initiation



Transcription Initiation

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14 Control of Gene Expression in Eukaryotes