G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis

Nirit Feldman, Ariela Gerson, Jia Fang, En Li, Yi Zhang, Yoichi Shinkai, Howard Cedar, Yehudit Bergman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

535 Scopus citations

Abstract

Oct-3/4 is a POU domain homeobox gene that is expressed during gametogenesis and in early embryonic cells, where it has been shown to be important for maintaining pluripotency. Following implantation, this gene undergoes a novel multi-step programme of inactivation. Transcriptional repression is followed by a pronounced increase in histone H3 methylation on Lys 9 that is mediated by the SET-containing protein, G9a. This step sets the stage for local heterochromatinization via the binding of HP1 and is required for subsequent de novo methylation at the promoter by the enzymes Dnmt3a/3b. Genetic studies show that these epigenetic changes actually have an important role in the inhibition of Oct-3/4 re-expression, thereby preventing reprogramming.

Original languageAmerican English
Pages (from-to)188-194
Number of pages7
JournalNature Cell Biology
Volume8
Issue number2
DOIs
StatePublished - Feb 2006

Bibliographical note

Funding Information:
We are grateful to T. Jenuwein for his cooperation. This work was supported by grants from the Israel Academy of Sciences (Y.B. and H.C.), Philip Morris USA Inc. and Philip Morris International (Y.B. and H.C), the National Institutes of Health (Y.Z., Y.B. and H.C.), the European Community 5th Framework Quality of Life Program (Y.B.), The American Cancer Society (Y.Z.), the Israel Cancer Research Fund (H.C.) and the Prostate Cancer Foundation (H.C.). COMPETING FINANCIAL INTERESTS The authors declare that they have no competing financial interests.

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