- 1.The fundamental of chemical physiology and of embryology is
to understand why tissue cells do not all express, all the time,
all the potentialities inherit in their genomeJACOB AND MONOD
DR.RITTU CHANDEL MD BIOCHEMISTRY (2ND YEAR) DEPARTMENT OF
BIOCHEMISTRY GRANT MEDICAL COLLEGE MUMBAI 06-08-13
2. functional unit of DNA Genome total genetic information
contained in cell Gene expression multistep process resulting in
production of functional gene product
GeneregulationprokaryoteseukaryotesLevelTranscriptionDNA level
Transcription Post transcription Translation Post
translationprocessfluctuatesirreversible 3. Itis absolutely
essential for growth, development, differentiation and very
existence of an organism It answers to if, how much and when
particular gene product is made Rapidly adjusts ( half life of mRNA
is low) eg. Insulin synthesized by pancreatic cell although nuclei
of all cells contain insulin gene 4. Housekeeping or constitutive
genes encode products required for basic cellular function
Continually expressed eg. Enzymes of TCA cycleInduction increase
the expression of particular product eg. Lac operon Repression
decreases the expression of particular product eg. Tryptophan
operon 5. Cistron smallest unit of genetic expression one cistron
one subunitOperon linear array of coordinately controlled
genes,turned on and off as a unitPromoters sequences that are
important for transcription most common rich in adenine and thymine
( TATA box ) other GC box, CAAregulatory sequence regulates
transcription embedded in NCR of genome cis acting when they
influence expression of gene on same chromosome 6. sugarLac
operonGlucose Lactose Glucose and lactoseOff ( negatively
regulated) On ( positively regulated) Off ( negatively regulated)
7. Nucleotide sequences of regulatory site shows a nearly perfect
inverted repeat, indicating that DNA in this region has an
approximately two fold axis of symmetrySymmetry matching is a
reccuring theme in DNA- protein interactions 8. Recognizespecific
DNA sequences 9. DNAbinding unit comes from protein lac repressor
Alpha helix from each monomer of protein is inserted into the major
groove of DNA, where amino acid side chains make specific contacts
with exposed edges of base pairs 10. These interactions allow the
lac repressor to bind more tightly to the specific site than to the
wide range of other sites present in E.coli genome 11. common to
many prokaryotic DNA BINDING PROTEINS Pair of alpha helices
separated by tight turn 2nd of these two helices is recognition
helix Residues of 1st helix participate in contacts with DNA
backbone exception- methionine repressor Is 12. Eg. Heme synthesis
regulated by repression of ALA synthase 13. p polatrpetrpdtrpb
trpctrpa 14. Genomelarger Nucleosome complex of DNA and histones
Not organized in operons Transcription and translation are
uncoupled Many different cell types present in most eukaryotes 15.
1.GeneamplificationEg- in fruitfly in resistance to methotrexate
16. DNAmethylases are base and sequence specific Prevents
transcription Heavily methylated genes not expressed 5 azacytidine
is inhibitor of methylases Housekeeping genes rarely methylated
Requirment 17. Chemicalmodification Most important in preventing
transcription Plays a role in maintenance of inactive chromatin Eg
barr body globin genes in non erythroid cells 18. Onegene is
switched off while a closely related gene takes up its function Hb
synthesis epsilon zeta (embryo) alpha gamma (6th month)alpha beta
(after birth) Immunoglobin synthesis IgM to IgG 19. At2 levels
1.chromosomal packaging Accessibility of transcription 2.individual
gene regulation 20. Requirementfor gene expression Chromatin
structure is modulated through covalent modifications of histone
tails Histone acetyltransferase (HAT) 21. Enhancerworks by
facilitating the binding of basic transcriptional complex to
promoter works when oriented in any direction exert positive
influence on transcription even when separated by 1000s of bp from
promoters 22. TranscriptionfactorsTranscription
factorsenhancerTranscription factorsTranscription
factorspromoterTranscription factors 23. Regulatedby signals eg.
Hormones Properties1.redundant 2.acts synergestically Have one
functional domain for DNA binding and one for transcription
activation Can be classified according to structure of their DNA
binding domains 24. Similarto prokaryotic helix turn helix
Recognizes asymetric DNA sequences 25. 2 cysteine and two histidine
residues seperated by 12 amino acids Cysteine residues are
seperated by 2 amino acids Histidine residues seperated by 3 amino
acids Loop that interacts with the major groove of DNA 26. 2
polypeptides join to form Y shaped dimer whose arms can interact
with major groove of DNA Stem leucine zipper Pair of long alpha
helices 1st part basic, makes contacts responsible for DNA
recognition site 2nd part - forms coiled coil structure with its
partner 27. BINDING MOTIFORGANISMREGULATORY PROTEINHELIX TURN
HELIXE.coliLac repressorZINC FINGERMammalsSteroid receptor
familyLEUCINE ZIPPERMammalsCRE binding protein 28.
Alternartivesplicing varied products are produced average human
genome is thought to code for 3 different proteins depending on
exons retained in splicing calcitonin gene 1.In thyroid gland 2.In
neurons 29. Mayoperate in nucleus or cytoplasm Nucleus hnRNA are
produced which is not processed to mRNA Cytoplasm vary considerably
in their half lives 30. Initiationfactors are involved Action of
initiation factor inhibited when phosphorylated by protein kinase
Eg. Reticulocytes no nuclei, must regulate synthesis of globin at
translational level When heme is high, globin is produced heme
prevents phosphorylation of initiation factors 31.
Modificationslike folding, enzymatic clevage or bond formation
Proinsulin -------------------- insulin Proteindegradation 32.
SATYANARYAN VASUDEVAN PANKAJANAIK LIPPINCOTT MARKS HARPER VOET
STRYERTHANK YOU
