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HYPERSENSITIVE SPOTS AND
ENHANCERS & BLOCKERS OF RNA
SYNTHESIS
By
Monisha Jayabalan
Ist MSc medical biochemistry
Dr.A.L.Mudaliar postgraduate institute of basic
medical sciences, University of Madras.
• hypersensitive site is a short region of chromatin and is
detected by its super sensitivity to cleavage by DNase I
and other various nucleases (DNase II and micrococcal
nucleases).
• the nucleosomal structure is less compacted.
• hypersensitive sites are found only in gene is being
expressed, and do not occur when the gene is inactive.
• Hypersensitive sites are generated as a result of the
binding of transcription factors that displace histone
octamers
ENHANCERS
• Enhancer sequences are regulatory DNA sequences that,
when bound by specific proteins called transcription
factors, enhance the transcription of an associated gene.
• Enhancer is a short region of about 50-1500 bp.
• Transcription factors can bind to enhancer sequences
located upstream or downstream from an associated
gene.
• enhancer sequences can be located thousands of base
pairs away from the transcription start site of the gene
being regulated.
• They are cis- acting
• It cannot act on the promoter region all by itself but by
binding with activator protein
• Enhancers can also be found within introns.
hypersensitive sites, enhancers and blockers of RNA synthesis
Enhanceosome
• higher-order protein complex assembled at the enhancer
and regulating expression of a target gene
• The binding and assembly of the activating proteins is
cooperative due to energetically favourable protein-
protein interactions formed in the complex.
Example : human interferon-beta gene
• Three activator proteins - NF-κB, an interferon activator
protein such as IRF-3, and the ATF-2/c-Jun complex -
cooperatively bind to the upstream enhancer region upon
viral infection.
• The interaction is mediated by a fourth protein HMG-I
hypersensitive sites, enhancers and blockers of RNA synthesis
BLOCKERS
Actinomycin D:
• elongation of RNA strands by RNA polymerase in bacteria
and eukaryotic RNA polymerases inhibitor.
• The planar portion of this molecule inserts (intercalates)
into the double helical DNA between successive G C base
pairs, deforming the DNA.
• Arcidine
Rifampicin
inhibits bacterial RNA synthesis by binding to the β subunit
of bacterial RNA polymerases, preventing the promoter
clearance step of transcription
hypersensitive sites, enhancers and blockers of RNA synthesis
• α-amanitin
• disrupts mRNA formation in animal cells by blocking Pol II
and, at higher concentrations Pol III.
• this is a toxic substance secreted by Amanita phalloides
hypersensitive sites, enhancers and blockers of RNA synthesis

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hypersensitive sites, enhancers and blockers of RNA synthesis

  • 1. HYPERSENSITIVE SPOTS AND ENHANCERS & BLOCKERS OF RNA SYNTHESIS By Monisha Jayabalan Ist MSc medical biochemistry Dr.A.L.Mudaliar postgraduate institute of basic medical sciences, University of Madras.
  • 2. • hypersensitive site is a short region of chromatin and is detected by its super sensitivity to cleavage by DNase I and other various nucleases (DNase II and micrococcal nucleases). • the nucleosomal structure is less compacted.
  • 3. • hypersensitive sites are found only in gene is being expressed, and do not occur when the gene is inactive. • Hypersensitive sites are generated as a result of the binding of transcription factors that displace histone octamers
  • 4. ENHANCERS • Enhancer sequences are regulatory DNA sequences that, when bound by specific proteins called transcription factors, enhance the transcription of an associated gene. • Enhancer is a short region of about 50-1500 bp. • Transcription factors can bind to enhancer sequences located upstream or downstream from an associated gene. • enhancer sequences can be located thousands of base pairs away from the transcription start site of the gene being regulated. • They are cis- acting
  • 5. • It cannot act on the promoter region all by itself but by binding with activator protein • Enhancers can also be found within introns.
  • 7. Enhanceosome • higher-order protein complex assembled at the enhancer and regulating expression of a target gene • The binding and assembly of the activating proteins is cooperative due to energetically favourable protein- protein interactions formed in the complex.
  • 8. Example : human interferon-beta gene • Three activator proteins - NF-κB, an interferon activator protein such as IRF-3, and the ATF-2/c-Jun complex - cooperatively bind to the upstream enhancer region upon viral infection. • The interaction is mediated by a fourth protein HMG-I
  • 10. BLOCKERS Actinomycin D: • elongation of RNA strands by RNA polymerase in bacteria and eukaryotic RNA polymerases inhibitor. • The planar portion of this molecule inserts (intercalates) into the double helical DNA between successive G C base pairs, deforming the DNA.
  • 12. Rifampicin inhibits bacterial RNA synthesis by binding to the β subunit of bacterial RNA polymerases, preventing the promoter clearance step of transcription
  • 14. • α-amanitin • disrupts mRNA formation in animal cells by blocking Pol II and, at higher concentrations Pol III. • this is a toxic substance secreted by Amanita phalloides