Regulation of Gene Expression ppt


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Khaled El Masry, is an assistant Lecturer of Human Anatomy & Embryology, Mansoura University, Egypt. Great thanks to Prof. Dr Salwa Gawish, professor of Cytology & Histology, Mansoura University, for her great effort in explaining Genetics course.

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Regulation of Gene Expression ppt

  1. 1. By: Khaled El MasryAssistant Lecturer of Human Anatomy & Embryology Mansoura Faculty of Medicine
  2. 2. A gene is the sequence of nucleotides in DNAencoding one polypeptide chain or one mRNAmolecule.Gene expression is carried out in 2 steps:1. transcription.2. translation.
  3. 3. 1. Environmental factors as heat and light.2. Signaling molecules as hormones and growthfactors.
  4. 4. HEAT: Exposure to high temperature Transcription of heat shock genes Synthesis of heat shock proteins Stabilize the internal cellular environment
  5. 5. LIGHT:In plants exposure to lightActivate transcription of the gene for Ribulose Carboxylase The enzyme that plays a critical role in PHOTOSYNTHESIS
  6. 6. HORMONES ”STEROID HORMONES” Hormone receptor complex Act as a transcription factor “PEPTIDE HORMONES” Activate a signaling system
  7. 7. 1. Regulatory elements: Promoters & Enhancers2. Transcription factors: Basal & Special
  8. 8. PromotersThe region necessary to initiate transcription.Consists of short nucleotide sequence that serveas the recognition point for binding of RNApolymerase.Located immediately adjacent to the genes theyregulate, upstream from the transcriptionstartpoint.
  9. 9. There are significant differences in number, orientation and distance between promotersin different genes.Promoters for RNA polymerase II include: TATA box, CAAT box, GC box, & Octamer box.Promoters for RNA polymerase & I III have adifferent sequence and bind differenttranscription factors.
  10. 10. Site Structure ImportanceTATA box 25-30 bp upstream 8 bp sequences Mutations in this (from the initial composed only of sequence greatly point of T=A pairs. reduce transcription transcription (Loosing the ability to bind to transcription factors)CAAT box 70-80 bp upstream CAAT or CCAAT Mutations in this (from the initial sequence. sequence greatly point of reduce transcription transcription GC box 110 bp upstream GGGCGG Documented by (from the initial sequence, often mutational analysis point of present in multiple transcription copies.Octamer box 120-130 bp ATTTGCAT Affects the upstream sequence. efficiency of (from the initial promoter in point of initiating transcription transcription.
  11. 11. DNA sequences interact with regulatory proteins increase the efficiency of initiation of transcription increase its rate.
  12. 12. Enhancers:Large >>>> up to several hundred bp long).Tissue- specific >>>> ( stimulate transcriptiononly in certain tissues).
  13. 13. 1. The proteins that bind to enhancers affect theactivity of proteins that bind to promoters.???2. Enhancers may allow RNA polymerase to bind toDNA and move along the chromosome till itreaches a promoter site.3. May respond to molecules outside the cell ( e.g :steroid hormones).4. May respond to molecules inside the cell ( e.g :during development thus the gene participates incell differentiation).
  14. 14. Enhancers bind to transcription factors by at Least 20 different proteins Form a complexchange the configuration of the chromatin folding, bending or looping of DNA.
  15. 15. DNA looping will bring the distal enhancersclose to the promoter site to form activatedtranscription complexes, then the transcriptionis activated, increasing the overall rate of RNAsynthesis.
  16. 16. 1. The enhancers affect the gene expressionindependent of their position or orientation.2. The enhancers operate from a distance awayfrom their target genes.
  17. 17. Def. :“ they are proteins essential for initiation of thetranscription, but they are not part of RNApolymerase molecule that carry out thetranscription process”.
  18. 18. Function:Each RNA polymerase requires a number oftranscription factors which help in:1. Binding of the enzyme to DNA template.2. Initiation and maintenance of transcription.3. Control the rate of gene expression.
  19. 19. These proteins contain 2 functional domains (a.asthat perform specific function).1. DNA binding domain: binds to DNA sequencespresent in regulatory regions (e.g : TATAbinding protein).2. Transcriptional activating domain: activatetranscription via protein-protein interaction
  20. 20. 1. Basal transcription factors: The initiation of transcription by RNApolymerase II requires the assistance of severalbasal transcription factors. Each of these proteins binds to a sequencewithin the promoter to facilitate the properalignment of RNA polymerase on the templatestrand of DNA.
  21. 21. The basal TFs must interact with the promoters inthe correct sequence to initiate transcriptioneffectively.TFIID is the 1st basal TF that interact with thepromoter ; it contains TATA- Binding Protein.Followed by TFII B, F, E, H & J.
  22. 22. 2. Special TFs:Involved in regulation of heat, light, and hormoneinducible genes.They bind to:a. enhancers.b. Basal TFs.c. RNA polymerase that bind to the genepromoter.Thus, special TFs can regulate thetranscriptional activity of the gene.
  23. 23. The normal structure of the chromatin suppressesthe gene activity, making the DNA relativelyinaccessible to transcription factors, and thusactive transcription complex can’t occur.Thus chromatin remodeling is needed( it is a change in chromatin conformation inwhich proteins of nucleosomes are releasedfrom DNA , allowing DNA to be accessible forTFs and RNA polymerase).
  24. 24. Inactive chromatin remodeled into activechromatin by 2 biochemical modifications:1. Acetylation of histone proteins by histone acetyltransferases which loosen the association betweenDNA and histone.2. Specialised protein complexes disrupt thenucleosome structure near the gene’s promotersite.( this protein complex slides histone along DNA transfer the histone to other location on DNA molecule.
  25. 25. Active chromatin can be deactivated by 3biochemical reactions:1. Histone deacetylation ( catalysed by histonedeacetylase).2. Histone methylation ( catalysed by histone methyltransferases).3. Methylation of some DNA nucleotides by DNAmethyl transferases.(Chromatin subjected to these modifications tends to betranscriptionaly silent)
  26. 26. siRNA & miRNAThese molecules 21-28 bp long.Able to interact with specific mRNA molecules.This interaction occurs by base pairing ( ) asingle strand of iRNA and a complementarysequence in the mRNA molecule.
  27. 27. siRNA miRNA Base pair perfectly with Base pair imperfectlythe target sequence in with the target mRNA sequence in mRNA mRNA cleavage and mRNA inhibition of degradation translation