Download MBBS Regulation of Gene Expression Lecture PPT

PRINCIPLES OF GENE REGULATION.

? INDUCTION AND REPRESSION. (ENHANCERS AND SILENCER).

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? HOUSEKEEPING AND INVISIBLE GENES.
? DNA ORGANISATION AND GENE EXPRESSION.
? GENOMIC ORGANOSATION ?SIZE AND GENE NUMBER.
? COVALENT MODIFICATION OF HISTONES CONTROL GENE

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EXPRESSION.

? DNA ?PROTEIN INTERACTIONS----
? PROTEIN MOTIFS-
? HELIX-TURN-HELIX

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? ZINC FINGER MOTIF
? LEUCINE ZIPPER MOTIF
?
DNA REGULATORY PROTEIN.

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? PROTEIN that regulate the gene expression include

repressors, inducers, enhancers, silencers, etc.

? They bind with specific region of DNA.

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? These protein have unique structure which allow them to bind

to target region.

? Some example are given below.......

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REGULATION OF GENE EXPRESSION IN

PROKARYOTES.

? INDUCTION AND REPRESSION- ENHANCERS AND SILENCERS---

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? Gene expression involves the transcription of a gene into mRNA

and the translation of the mRNA into protein.

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? At any given time , only a fraction of the genome is expressed.

? Gene expression is induced by positive regulatory

elements(inducers or enhancers).

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? Can be decreased or blocked by negative regulations (repressors or

silencers).
? There are many gene which are not subjected to

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regulation. e.g.- the enzymes of the Krebs cycle. Such

genes are known as constitutive or housekeeping

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genes.

? Other group of genes are regulated by inducers or

repressors as per cellular needs are called inducible

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genes.
? Most of the DNA is associated with specific class of

proteins known as histones to form a structure called

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nucleosome.

? INTRONS- intervening sequence.

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? EXONS---coding region.
COVALENT MODIFICATION OF HISTONES

CONTROL GENE EXPRESSION.

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? Histone proteins by undergoing covalent

modifications (acetylation, methylation,

phosphorylation) exert control over gene expression.

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? Acetylation of histones promotes gene expression

while deacetylation represses it.

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? Methylation on some DNA sequences, blocks gene

expression.
DNA-Protein interactions.

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? Certain proteins bind to specific sequences on the DNA and

regulate transcription.

? These are known as regulatory protein which have a high

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binding affinity to the control site on DNA.

? The DNA ? protein are mediated by certain motifs.
? Three types of protein motifs.

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? 1.Helix-turn-helix motif.

? 2.Zinc finger motif.

? 3.Leucine zipper motif.

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HELIX-TURN-HELIX MOTIF

? The helix-turn-helix motif is made up of about 20 amino acids

organised into two a-helices separated by a B-sheet.

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? Lac repressor, tryptophan repressor and cyclic AMP

catabolite activator protein (CAP) of E . coli and several

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regulatory proteins in mammalian cells act via this DNA-

binding motif.
ZINC FINGER MOTIF

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? Many regulatory proteins eukaryotic cells
contain multiple zinc fingers (e.g. TF IIIA).

? The receptors of group l hormones (steroid
and thyroids) contain zinc fingers.

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? A mutation involving a single amino acid in a
zinc finger of calcitriol receptor protein
interferes with its function and results in
rickets.
LEUCINE ZIPPER MOTIF.

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? Regulatory proteins with leucine zipper motifs

contain a large number of basic amino acids (Lys and

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Arg ), which associate with the negatively

phosphates of the DNA molecule.

? The a-helices of this motif contain the amino

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acid leucine at every seventh position.

? Many regulatory proteins contain this type of motif

(e.g. The enhancer binding proteins- FOS and JUN).

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REGULATION OF GENE EXPRESSION IN

PROKARYOTES.

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? Operon concept-
To explain how genes are regulated in prokaryotes.
The expression of structure gene encoding protein is under

control of regulatory gene.

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The regulatory element and and protein ? encoding genes act

in a well orchestrated manner and function as a single unit

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called Operon.

Operon-
Operon can be considered as a coordinated unit of gene

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expression in prokaryotes.
LAC OPERON.

? MECHANISM OF REPRESSI ON--
? When glucose is

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available to the E. Coli bacteria , lac Z, Y and A,

Genes are repressed.

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? They are not transcribed, This is mediated by

repressor.

? Repressor bind to operator, Repressor binding

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interferes with the RNA polymerase binding and

prevent transcription of structural genes--lacA, lac

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Z and lac Y.
LAC OPERON

? MECHANISM OF INDUCTION
? Absence of glucose induces the

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lac operon to transcribe the three enzymes gene i.e.-Z , Y and

A.

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? The induced enzyme then act on lactose to produce

allolactose, the actual inducer of lac operon.

? Inducer bind to repressor molecule , and induce a

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conformational change in repressor. Repressor does not bind

to the operator , Now RNA polymerase can bind with DNA

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and initiate transcription.

? RNA polymerase requires the binding of cAMP and

CAP(catabolic gene activator protein) complex.

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ANABOLIC OPERON.

? TRYPTOPHAN OPERON-
? Gene of anabolic pathway such as

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synthesis of aminoacid are also regulated by operon.

? Tryptophan operon is one such example seen in E. Coli,

depending on the concentration of tryptophan in cell,and

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when there is deficiency , transcription is allowed.


LAC OPERON.(Jacob and Monod).

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? Most bacteria, such as E.coli, utilise glucose as the fuel source . But

when glucose is unavailable ,E. Coli uses lactose as the alternative

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fuel source.

? Regulation of lactose metabolism in E. Coli.

? Three enzymes are involved in the lactose metabolism.

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? Beta galactosidase.

? Permease.

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? Transacetylase.

STRUCTURE OF LAC OPERON.

Lac operon

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Regulatory gene(I)

Operator

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gene(O)

Z structural

Y structural

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A structural

gene

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gene

gene
? Apart from structural gene (Z Y A ) the operon also contain a

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promoter site (P ).

? Operator site directs the RNA polymerase to the correct

transcription start site.

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? The Z , Y , and A genes are transcribed into a single large

mRNA that encodes for the three enzymes.

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GENE REGULATION IN EUKARYOTES.

? 1.chromatin structure.
? 2.Gene amplification.
? 3.Gene rearrangement.

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? 4.Regulatory element.
5.Transcriptional control.
? 6.RNA processing control.
? 7.RNA transport and localisation control.
? 8.Translation control.

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? 9.mRNA degradation.
? 10.protein activator control/ Gene regulation at the level of

translation.

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? 1.Chromatin structure and gene regulation-

covalent modification on Histone protein remodel

chromatin and make it more transcription friendly.

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2. Gene amplification-

An amplification of a few pre-existing gene occurs,

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resulting in formation of desired proteins.

3. Gene rearrangement--synthesis of antibodies.

4. Rgulatory element--

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Promoter element-role in initiating the

transcription by recruiting the RNA polymerase at the correct site on the

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gene.

TATA box.

Hormone responsive element.

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Enhancers.

Repressors.
? 5.Transcription factors-

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? various transcription factors (TFIIA, TFIIB,

TFIID, TFIIE....) assembledb in a specific sequence to form a

preinitiation complex.

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? 6.RNA processing?
? post-transcriptional modification to form

mature mRNA.

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? 7.m RNA splicing......
? 8.Transport of mRNA.
? 9.Gene regulation and translation---Gene regulation can be

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regulated at the level of translation.

? The gene encoding transferrin , ferritin, and hemosiderin.
? Regulation by RNA editing-
? ApoB100 to Apo B 48.

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? Tissue specific Expression by Enhancer--
? Enhanced

expression of immunoglobulin genes is seen in

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plasma cell produced from activated B lymphocytes

but not in other cell.