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DCAF 13 promotes pluripotency by negatively regulating SUV 39H1 stability during early embryonic development
Author(s) -
Zhang YinLi,
Zhao LongWen,
Zhang Jue,
Le Rongrong,
Ji ShuYan,
Chen Chuan,
Gao Yawei,
Li Dali,
Gao Shaorong,
Fan HengYu
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201898981
Subject(s) - biology , embryonic stem cell , microbiology and biotechnology , genetics , gene
Mammalian oocytes and zygotes have the unique ability to reprogram a somatic cell nucleus into a totipotent state. SUV 39H1/2‐mediated histone H3 lysine‐9 trimethylation (H3K9me3) is a major barrier to efficient reprogramming. How SUV 39H1/2 activities are regulated in early embryos and during generation of induced pluripotent stem cells ( iPSC s) remains unclear. Since expression of the CRL 4 E3 ubiquitin ligase in oocytes is crucial for female fertility, we analyzed putative CRL 4 adaptors ( DCAF s) and identified DCAF 13 as a novel CRL 4 adaptor that is essential for preimplantation embryonic development. Dcaf13 is expressed from eight‐cell to morula stages in both murine and human embryos, and Dcaf13 knockout in mice causes preimplantation‐stage mortality. Dcaf13 knockout embryos are arrested at the eight‐ to sixteen‐cell stage before compaction, and this arrest is accompanied by high levels of H3K9me3. Mechanistically, CRL 4‐ DCAF 13 targets SUV 39H1 for polyubiquitination and proteasomal degradation and therefore facilitates H3K9me3 removal and zygotic gene expression. Taken together, CRL 4‐ DCAF 13‐mediated SUV 39H1 degradation is an essential step for progressive genome reprogramming during preimplantation embryonic development.