Related Experiment Videos
CTCF elements direct allele-specific undermethylation at the imprinted H19 locus
Eyal Rand1, Ittai Ben-Porath, Ilana Keshet
1Department of Cellular Biochemistry, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel.
Current Biology : CB
|June 9, 2004
Summary
CCCTC binding factor (CTCF) protects the maternal H19 gene allele from methylation. This mechanism maintains the unique imprinting control region (ICR) pattern, crucial for gene regulation throughout development.
Area of Science:
- Genetics and Epigenetics
- Molecular Biology
- Developmental Biology
Background:
- The H19 imprinted gene locus is controlled by an imprinting control region (ICR).
- This ICR exhibits allele-specific DNA methylation, established during gametogenesis.
- The maternal ICR is unmethylated, while the paternal ICR is methylated during spermatogenesis.
Purpose of the Study:
- To investigate the mechanism protecting the maternal H19 allele from de novo methylation.
- To understand how allele-specific methylation patterns are maintained during early development.
Main Methods:
- Genetic approach using transfection into embryonic stem (ES) cells.
- Analysis of CCCTC binding factor (CTCF) interactions with the ICR.
Main Results:
- CCCTC binding factor (CTCF) boundary elements within the ICR prevent maternal allele methylation.
- CTCF binding is sequence-specific and disrupted by methylation.
- This differential binding preserves the gamete-derived, allele-specific methylation pattern.
Conclusions:
- CTCF plays a critical role in maintaining the unmethylated state of the maternal H19 allele.
- CTCF acts as a barrier to de novo methylation at the ICR.
- CTCF may have a general function in preserving differential methylation patterns in vivo.