This document discusses methylation of the MeCP2 gene and its potential intergenerational effects. It covers: 1) MeCP2 is a methyl-CpG binding protein involved in transcriptional repression. Mutations can cause Rett syndrome. 2) The structure and function of the MeCP2 protein, which binds to methylated DNA and recruits histone deacetylases to repress gene transcription. 3) The study aims to analyze relationships between maternal smoking, MeCP2 gene methylation levels, and baby phenotypes like weight, length and gestational age.

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!!!!