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CTCF and Imprinting Disorder

CTCF and Imprinting Disorder. Preeti Misra Sang-Gook Han. Contents. Interesting Protein and Diseases. Background. Gene Network. Properties of CTCF. Epigenetic - Acetylation - Methylation. Pathway - CTCF. Human diseases. Loss of Imprinting. U(t). Y(t). +. C(t). P(t).

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CTCF and Imprinting Disorder

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  1. CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han

  2. Contents Interesting Protein and Diseases Background • Gene Network • Properties of CTCF • Epigenetic • - Acetylation • - Methylation • Pathway - CTCF • Human diseases • Loss of Imprinting

  3. U(t) Y(t) + C(t) P(t) + - H(t) Background: Gene Network • Activation and Inhibition with evolution Control: Achieve an objective of the system Survival, reproduction

  4. Background: Epigenetic Epigenetic : Surface of genetic Gene expression control without modification of DNA sequence. • Histone Modification • Acetylation • Methylation DNA Methylation - Methylation of Cystosine(C). - CpG island Expansion Condensation

  5. Background: Epigenetic

  6. DNA Methylation • Post-synthetic modifications of Chromatin structure • Cytosine-Guanine (CG) base pair is methylated. • Regulation in gene expression.

  7. Background: Loss of epigenetic marks.

  8. Background: Genomic Imprinting DMR: Differentially Methylated Region ICR: Imprinting Control Region father mother

  9. CTCF Protein • Gene location: 16q22 • 11 zinc fingers. • Transcription Binding Factor : (MYC, PLK, PIM-1, p19ARF, and Igf2/H19, APPβ,β-globin, and lysozyme regulatory sequences ) • Binding to TFBSs including ICR and CpG island. • Cis-regulartory. • Regulation of DNA methylation pattern • Highly conserved. • There are 39,622 ZnFg registered in pFam

  10. CTCF motif

  11. CTCF Structure Classification and GO

  12. CTCF Protein : C2H2 type C - x(2,4) - C - x(3) - [LIVMFYWC] - x(8) - H - x(3,5) – H GSSGSSGRTHTGEKPYACSHCDKTFRQKQLLDMHFKRYHDPNFVPAAFVCSKCGKTFTRRNTMARHADNCAGPDGVEGENSGPSSG

  13. CTCF and its Uses • CTCF is involved in the control of cell growth and differentiation. • Involved in IGF2 imprinting regulation. • CTCF may represent a novel tumor suppressor gene that displays tumor-specific "change of function" rather than complete "loss of function“. • CTCF may establishes a regulatable epigenetic switch for X-inactivation

  14. Human Disease: Beckwith-Wiedemann syndrome BWS locus: 11p15.5 BWS occurs in 1:13,700 Phenotypes: 1. Macroglossia: Problem with Eating, Breathing, speaking 2. Abdominal wall defects 3. Fast growth: birth weight and height (above mean) enlarge internal organs (kidneys, liver,pancreas) hemihyperplasia 4. Ear lobe

  15. Pathway : BWS BWS Tumor Wilms’ Tumor CTCF Inhibit the enhancer from activating IGF2(Insulin-like Growth Factor 2) and causes H19 to be expressed.

  16. Mutation ZF3 ZF3 ZF3 ZF7

  17. Other Diseases • Prader-Willis Syndrome(PWS)-failure to thrive during infancy and hyperphagia. • Angelman syndrome(AS)- mental retardation and speech impairment • Transient neonatal diabetes mellitis(TNDM)-a rare form of diabetes • Alpha-thalassemiaoccurs(males)- mental retardation syndrome.

  18. Capta

  19. Capta

  20. Catpa

  21. Reference • http://www.benbest.com/health/cancer.html • http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10664 • Marcus Vinicius de Matos Gomes; Ester Silveira Ramos (2003), Beckwith-Wiedemann syndrome and isolated hemihyperplasia, Sao Paulo Med J. 21, 133-138 • Keith D. Robertson (2004), DNA Methylation and Human Disease, Nature, 6, 597-610 • Galina N. Filippova, et. al. (2002), Tumor-associated Zinc Finger Mutations in the CTCF Transcription Factor Selectively Alter Its DNA-binding Specificity, Cancer Research, 62, 48-52

  22. Question Time!!!!

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