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