1. 흡연에 따른 MeCP2 유전자의
메틸화와 후성유전학적 평가
제일병원 유전학연구실 김진우

2.  DNA methylation
 major modification of eukaryotic genomes
plays an essential role in mammalian development
 CpG 결합 단백질
: MECP2, MBD1, MBD2, MBD3, and MBD4
: capable of binding specifically to methylated DNA
: repress transcription from methylated gene promoters

4.  MeCP2 gene
 methyl CpG binding protein 2 (Rett syndrome)
 making its protein product, MECP2
 located on Xq28
 essential for the normal function of nerve cells
 important for mature nerve cells (high levels)
 turning off ("repressing" or "silencing") several other
genes
 X-linked and subject to X inactivation
 dispensable in stem cells
 mutations
- a progressive neurologic developmental disorder
- mental retardation in females

5.  McCP2; Structure
 a family of methyl-CpG-binding domain (MBD)
 two functional domains:
1. a methyl-cytosine-binding domain (MBD)
- composed of 85 amino acids
- forms a wedge
- attaches to the DNA strands
2. a transcriptional repression domain (TRD)
- composed of 104 amino acids
- recruit histone deacetylases (HDAC)
 carboxyl terminus: unusual, repetitive
sequences

6.  MeCP2; Function
 found in all cells in the body, including the brain
 acting as a transcriptional repressor and activator
 as an activator: controversial
 In the brain,
found in high concentrations in neurons
maturation of the central nervous system (CNS)
forming synaptic contacts

7.  MeCP2; Mechanism
 binds to forms of methylated CpG islands of promotors
 form a complex that turns off the gene
 not yet determined which genes are targeted by the MeCP2 protein
 probably important for the normal function of the central nervous
system
 form a complex with histone deacetylases (HDAC)
block transcription factors directly

8.  Objectives
Phenotype
MeCP2 gene - baby weight
Hypo - methylation - baby length
Hyper - methylation
- head length
???
- gestation week
Smoking - IUGR

9.  Study schedule
Epigenetic variation
DNA methylation
- MeCP2 gene Phenotype
- baby weight
- baby length
- Head length
- Gestation week
- IUGR
 Statistical analysis
Smoking – baby’s phenotype
Smoking – MeCP2 methylation
MeCP2 methylation – baby’s phenotype

10. Thanks you!!!!