CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.
-
Upload
paulina-parrish -
Category
Documents
-
view
220 -
download
0
Transcript of CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.
![Page 1: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/1.jpg)
CTCF and CTCF and Imprinting Imprinting DisorderDisorder
Preeti MisraSang-Gook
Han
![Page 2: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/2.jpg)
Contents
•Gene Network
•Epigenetic - Acetylation - Methylation
•Properties of CTCF
•Pathway - CTCF
•Human diseases
Background Interesting Protein and Diseases
•Loss of Imprinting
![Page 3: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/3.jpg)
Background: Gene Network
• Activation and Inhibition with evolution
Control: Achieve an objective of the system
Survival, reproduction
P(t)
H(t)
+U(t) Y(t)
-
+C(t)
![Page 4: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/4.jpg)
Background: EpigeneticEpigenetic : 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
![Page 5: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/5.jpg)
Background: Epigenetic
![Page 6: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/6.jpg)
DNA Methylation
• Post-synthetic modifications of Chromatin structure
• Cytosine-Guanine (CG) base pair is methylated.
• Regulation in gene expression.
![Page 7: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/7.jpg)
Background: Loss of epigenetic marks.
![Page 8: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/8.jpg)
Background: Genomic Imprinting
DMR: Differentially Methylated RegionICR: Imprinting Control Region
father
mother
![Page 9: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/9.jpg)
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
![Page 10: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/10.jpg)
CTCF motif
![Page 11: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/11.jpg)
CTCF Structure Classification and GO
![Page 12: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/12.jpg)
C - x(2,4) - C - x(3) - [LIVMFYWC] - x(8) - H - x(3,5) – HGSSGSSGRTHTGEKPYACSHCDKTFRQKQLLDMHFKRYHDPNFVPAAFVCSKCGKTFTRRNTMARHADNCAGPDGVEGENSGPSSG
CTCF Protein : C2H2 type
![Page 13: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/13.jpg)
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
![Page 14: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/14.jpg)
Human Disease: Beckwith-Wiedemann
syndromeBWS 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
![Page 15: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/15.jpg)
Pathway : BWS
CTCF Inhibit the enhancer from activating IGF2(Insulin-like Growth Factor 2) and causes H19 to be expressed.
Wilms’ Tumor BWS Tumor
![Page 16: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/16.jpg)
Mutation
ZF3 ZF3 ZF3 ZF7
![Page 17: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/17.jpg)
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.
![Page 18: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/18.jpg)
Capta
![Page 19: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/19.jpg)
Capta
![Page 20: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/20.jpg)
Catpa
![Page 21: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/21.jpg)
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
![Page 22: CTCF and Imprinting Disorder Preeti Misra Sang-Gook Han.](https://reader035.fdocuments.in/reader035/viewer/2022070410/56649edf5503460f94bef937/html5/thumbnails/22.jpg)
Question Time!!!!