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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting
Andrew M Fedoriw1, Paula Stein, Petr Svoboda
1Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science (New York, N.Y.)
|January 13, 2004
Summary
The CCCTC binding factor (CTCF) protein protects the H19 differentially methylated domain (DMD) from methylation during oocyte growth. CTCF deficiency in oocytes impairs their development and H19 DMD methylation.
Area of Science:
- Epigenetics
- Developmental Biology
- Genomics
Background:
- Imprinted gene regulation, specifically of H19 and Insulin-like growth factor 2 (IGF2), relies on the CCCTC binding factor (CTCF) interacting with a differentially methylated domain (DMD).
- The mechanisms maintaining the hypomethylated state of the H19 DMD during oogenesis and CTCF's role in this process remain unclear.
Purpose of the Study:
- To investigate the role of CTCF in maintaining the hypomethylated state of the H19 differentially methylated domain (DMD) during oogenesis.
- To determine the impact of CTCF deficiency on oocyte methylation and developmental competence.
Main Methods:
- Utilized a transgenic RNA interference (RNAi) approach to create oocytes with reduced CTCF protein levels.
- Assessed methylation status of the H19 DMD and evaluated the developmental competence of CTCF-deficient oocytes.
Main Results:
- Oocytes with reduced CTCF protein exhibited increased methylation of the H19 DMD.
- CTCF-deficient oocytes displayed decreased developmental competence, indicating impaired preimplantation development.
- CTCF appears to play a protective role against de novo methylation at the H19 DMD during oocyte growth.
Conclusions:
- CTCF is essential for protecting the H19 differentially methylated domain (DMD) from de novo methylation during oocyte development.
- CTCF is required for normal preimplantation development, highlighting its critical role in early embryogenesis.
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