Download CTCF and Human Disease

CTCF and
Imprinting Disorder
Preeti Misra
Sang-Gook Han
Contents
Background
Interesting Protein
and Diseases
•Gene Network
•Epigenetic
- Acetylation
- Methylation
•Loss of Imprinting
•Properties of CTCF
•Pathway - CTCF
•Human diseases
Background: Gene Network
• Activation and Inhibition with evolution
Control: Achieve an objective of the system
Survival, reproduction
U(t)
+
Y(t)
+
C(t)
P(t)
-
H(t)
Background: Epigenetic
Epigenetic : Surface of genetic
Gene expression control without modification
of DNA sequence.
Histone Modification
–Acetylation
–Methylation
Expansion Condensation
DNA Methylation
- Methylation of Cystosine(C).
- CpG island
Background: Epigenetic
DNA Methylation
• Post-synthetic modifications of Chromatin
structure
• Cytosine-Guanine (CG) base pair is methylated.
• Regulation in gene expression.
Background:
Loss of epigenetic marks.
Background:
Genomic Imprinting
father
mother
DMR: Differentially Methylated Region
ICR: Imprinting Control Region
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
CTCF motif
CTCF Structure
Classification and GO
CTCF Protein : C2H2 type
C - x(2,4) - C - x(3) - [LIVMFYWC] - x(8) - H - x(3,5) – H
GSSGSSGRTHTGEKPYACSHCDKTFRQKQLLDMHFKRYHDPNFVPAAFVCS
KCGKTFTRRNTMARHADNCAGPDGVEGENSGPSSG
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
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
Pathway : BWS
Wilms’ Tumor
BWS Tumor
CTCF Inhibit the enhancer from activating
IGF2(Insulin-like Growth Factor 2) and causes H19
to be expressed.
Mutation
ZF3
ZF3
ZF3
ZF7
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.
Capta
Capta
Catpa
Reference
•
http://www.benbest.com/health/cancer.html
•
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Gr
aphics&list_uids=10664
•
Marcus Vinicius de Matos Gomes; Ester Silveira Ramos (2003), BeckwithWiedemann syndrome and isolated hemihyperplasia, Sao Paulo Med J. 21, 133138
•
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
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