Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Regulation of Gene Expression Lecture PPT
PRINCIPLES OF GENE REGULATION.
? INDUCTION AND REPRESSION. (ENHANCERS AND SILENCER).
? HOUSEKEEPING AND INVISIBLE GENES.
? DNA ORGANISATION AND GENE EXPRESSION.
? GENOMIC ORGANOSATION ?SIZE AND GENE NUMBER.
? COVALENT MODIFICATION OF HISTONES CONTROL GENE
EXPRESSION.
? DNA ?PROTEIN INTERACTIONS----
? PROTEIN MOTIFS-
? HELIX-TURN-HELIX
? ZINC FINGER MOTIF
? LEUCINE ZIPPER MOTIF
?
DNA REGULATORY PROTEIN.
? PROTEIN that regulate the gene expression include
repressors, inducers, enhancers, silencers, etc.
? They bind with specific region of DNA.
? These protein have unique structure which allow them to bind
to target region.
? Some example are given below.......
REGULATION OF GENE EXPRESSION IN
PROKARYOTES.
? INDUCTION AND REPRESSION- ENHANCERS AND SILENCERS---
? Gene expression involves the transcription of a gene into mRNA
and the translation of the mRNA into protein.
? At any given time , only a fraction of the genome is expressed.
? Gene expression is induced by positive regulatory
elements(inducers or enhancers).
? Can be decreased or blocked by negative regulations (repressors or
silencers).
? There are many gene which are not subjected to
regulation. e.g.- the enzymes of the Krebs cycle. Such
genes are known as constitutive or housekeeping
genes.
? Other group of genes are regulated by inducers or
repressors as per cellular needs are called inducible
genes.
? Most of the DNA is associated with specific class of
proteins known as histones to form a structure called
nucleosome.
? INTRONS- intervening sequence.
? EXONS---coding region.
COVALENT MODIFICATION OF HISTONES
CONTROL GENE EXPRESSION.
? Histone proteins by undergoing covalent
modifications (acetylation, methylation,
phosphorylation) exert control over gene expression.
? Acetylation of histones promotes gene expression
while deacetylation represses it.
? Methylation on some DNA sequences, blocks gene
expression.
DNA-Protein interactions.
? Certain proteins bind to specific sequences on the DNA and
regulate transcription.
? These are known as regulatory protein which have a high
binding affinity to the control site on DNA.
? The DNA ? protein are mediated by certain motifs.
? Three types of protein motifs.
? 1.Helix-turn-helix motif.
? 2.Zinc finger motif.
? 3.Leucine zipper motif.
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.
? Lac repressor, tryptophan repressor and cyclic AMP
catabolite activator protein (CAP) of E . coli and several
regulatory proteins in mammalian cells act via this DNA-
binding motif.
ZINC FINGER MOTIF
? 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.
? 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.
? Regulatory proteins with leucine zipper motifs
contain a large number of basic amino acids (Lys and
Arg ), which associate with the negatively
phosphates of the DNA molecule.
? The a-helices of this motif contain the amino
acid leucine at every seventh position.
? Many regulatory proteins contain this type of motif
(e.g. The enhancer binding proteins- FOS and JUN).
REGULATION OF GENE EXPRESSION IN
PROKARYOTES.
? Operon concept-
To explain how genes are regulated in prokaryotes.
The expression of structure gene encoding protein is under
control of regulatory gene.
The regulatory element and and protein ? encoding genes act
in a well orchestrated manner and function as a single unit
called Operon.
Operon-
Operon can be considered as a coordinated unit of gene
expression in prokaryotes.
LAC OPERON.
? MECHANISM OF REPRESSI ON--
? When glucose is
available to the E. Coli bacteria , lac Z, Y and A,
Genes are repressed.
? They are not transcribed, This is mediated by
repressor.
? Repressor bind to operator, Repressor binding
interferes with the RNA polymerase binding and
prevent transcription of structural genes--lacA, lac
Z and lac Y.
LAC OPERON
? MECHANISM OF INDUCTION
? Absence of glucose induces the
lac operon to transcribe the three enzymes gene i.e.-Z , Y and
A.
? The induced enzyme then act on lactose to produce
allolactose, the actual inducer of lac operon.
? Inducer bind to repressor molecule , and induce a
conformational change in repressor. Repressor does not bind
to the operator , Now RNA polymerase can bind with DNA
and initiate transcription.
? RNA polymerase requires the binding of cAMP and
CAP(catabolic gene activator protein) complex.
ANABOLIC OPERON.
? TRYPTOPHAN OPERON-
? Gene of anabolic pathway such as
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
when there is deficiency , transcription is allowed.
LAC OPERON.(Jacob and Monod).
? Most bacteria, such as E.coli, utilise glucose as the fuel source . But
when glucose is unavailable ,E. Coli uses lactose as the alternative
fuel source.
? Regulation of lactose metabolism in E. Coli.
? Three enzymes are involved in the lactose metabolism.
? Beta galactosidase.
? Permease.
? Transacetylase.
STRUCTURE OF LAC OPERON.
Lac operon
Regulatory gene(I)
Operator
gene(O)
Z structural
Y structural
A structural
gene
gene
gene
? Apart from structural gene (Z Y A ) the operon also contain a
promoter site (P ).
? Operator site directs the RNA polymerase to the correct
transcription start site.
? The Z , Y , and A genes are transcribed into a single large
mRNA that encodes for the three enzymes.
GENE REGULATION IN EUKARYOTES.
? 1.chromatin structure.
? 2.Gene amplification.
? 3.Gene rearrangement.
? 4.Regulatory element.
5.Transcriptional control.
? 6.RNA processing control.
? 7.RNA transport and localisation control.
? 8.Translation control.
? 9.mRNA degradation.
? 10.protein activator control/ Gene regulation at the level of
translation.
? 1.Chromatin structure and gene regulation-
covalent modification on Histone protein remodel
chromatin and make it more transcription friendly.
2. Gene amplification-
An amplification of a few pre-existing gene occurs,
resulting in formation of desired proteins.
3. Gene rearrangement--synthesis of antibodies.
4. Rgulatory element--
Promoter element-role in initiating the
transcription by recruiting the RNA polymerase at the correct site on the
gene.
TATA box.
Hormone responsive element.
Enhancers.
Repressors.
? 5.Transcription factors-
? various transcription factors (TFIIA, TFIIB,
TFIID, TFIIE....) assembledb in a specific sequence to form a
preinitiation complex.
? 6.RNA processing?
? post-transcriptional modification to form
mature mRNA.
? 7.m RNA splicing......
? 8.Transport of mRNA.
? 9.Gene regulation and translation---Gene regulation can be
regulated at the level of translation.
? The gene encoding transferrin , ferritin, and hemosiderin.
? Regulation by RNA editing-
? ApoB100 to Apo B 48.
? Tissue specific Expression by Enhancer--
? Enhanced
expression of immunoglobulin genes is seen in
plasma cell produced from activated B lymphocytes
but not in other cell.
This post was last modified on 30 November 2021