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Published on: December 12, 2019
DNMT1 interacts with the developmental transcriptional repressor HESX1
Ezat Sajedi1, Carles Gaston-Massuet, Cynthia L Andoniadou
1Neural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, WC1N 1EH, London, UK.
Biochimica Et Biophysica Acta
|October 13, 2007
Summary
The homeobox gene HESX1 is crucial for brain and pituitary development. Researchers discovered HESX1 interacts with DNA methyltransferase 1 (DNMT1), suggesting a new role for HESX1 in gene repression.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Epigenetics
Background:
- HESX1 (Hesx1) is a conserved vertebrate homeobox gene essential for forebrain and pituitary development.
- Mutations in human HESX1 cause developmental defects similar to those in Hesx1-deficient mice.
Purpose of the Study:
- To elucidate the molecular function of HESX1.
- To identify proteins interacting with HESX1.
Main Methods:
- Yeast two-hybrid screening to identify HESX1 binding partners.
- Co-expression analysis in mouse tissues.
- Interaction mapping and co-immunoprecipitation assays.
Main Results:
- DNA methyltransferase 1 (DNMT1) was identified as a HESX1 binding protein.
- Dnmt1 and Hesx1 are co-expressed in the anterior forebrain and Rathke's pouch.
- HESX1 binds to the N-terminus and catalytic domain of DNMT1; complexes co-localize in the nucleus.
Conclusions:
- Establishes a molecular link between HESX1 and DNMT1.
- Suggests a novel mechanism for HESX1's transcriptional repressor activity involving DNMT1.
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