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Setd5, but not Setd2, is indispensable for retinal cell survival and proliferation
Toshiro Iwagawa1,2, Ryoko Kawabata1,2, Masaya Fukushima1,2
1Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Japan.
FEBS Letters
|November 9, 2022
Summary
Setd5 is crucial for retinal development, impacting cell survival and proliferation. Setd2 is not essential, and Setd5
Area of Science:
- Molecular Biology
- Developmental Biology
- Epigenetics
Background:
- Histone trimethylation, specifically H3K36me3, is linked to active gene transcription.
- Setd2 and Setd5 are known H3K36me3 methyltransferases, but their roles in retinal development are not fully understood.
Purpose of the Study:
- To investigate the specific roles of Setd5 and Setd2 in mouse retinal development.
- To elucidate the functional domains of SETD5 critical for retinal cell survival and proliferation.
Main Methods:
- Utilized mouse retinal explant cultures.
- Employed short hairpin RNA (shRNA) to knockdown Setd2 and Setd5 expression.
- Generated and tested SETD5 mutants lacking the SET domain or specific interaction sites.
Main Results:
- Knockdown of Setd5 (shSetd5) resulted in abnormal retinal structures and reduced populations of rod photoreceptors and Müller cells.
- Knockdown of Setd2 (shSetd2) did not induce any observable retinal abnormalities.
- A SETD5 mutant lacking the SET domain could not rescue shSetd5-induced retinal phenotypes.
- A SETD5 mutant (SETD5S1257*) that disrupts interaction with HDAC3 and PAF1 complexes partially rescued proliferation but not apoptosis.
Conclusions:
- Setd5, unlike Setd2, is essential for maintaining retinal cell survival and proliferation during development.
- The SET domain of SETD5 is critical for its function in supporting retinal cell survival and proliferation.
