Setd5, but not Setd2, is indispensable for retinal cell survival and proliferation. Issue 3 (22nd November 2022)

• Record Type: Journal Article
• Authors: Iwagawa, Toshiro; Kawabata, Ryoko; Fukushima, Masaya; Kuribayashi, Hiroshi; Watanabe, Sumiko
• Is Part Of: FEBS letters. Volume 597:Issue 3(2023)
• Page Start: 427
• Page End: 436
• Publication Date: 2022-11-22
• Subjects: H3K36me3 -- retinal development -- Setd2 -- Setd5; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14537
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Trimethylation of histone H3 at lysine 36 (H3K36me3) is associated with active transcription. We used mouse retinal explant cultures and shRNA to investigate the roles of Setd2 and Setd5, which encode H3K36me3 methyltransferases, in retinal development. We found that shSetd5 caused abnormal retinal structures and reduced rods and Müller cells, whereas shSetd2 did not cause any abnormalities. The mutant SETD5 lacking the SET domain failed to reverse the phenotypes observed in the shSetd5‐expressing retinas, while SETD5S1257*, which does not interact with HDAC3 and PAF1 complexes, rescued proliferation, but not apoptosis, induced by shSetd5. Taken together, we found that Setd5, but not Setd2, is essential for sustaining retinal cell survival and proliferation, and the SET domain of SETD5 is pivotal for both functions. Abstract : We investigated the roles of the histone methyltransferases Setd2 and Setd5, which mediate trimethylation of histone H3 at lysine 36 (H3K36me3), in retinal development. Results suggest that the Su(var)3–9, enhancer‐of‐zeste, Trithorax (SET) domain of SETD5 is pivotal for sustaining retinal cell survival and proliferation, and the interaction of SETD5 with HDAC3 and PAF1 complexes is essential for retinal cell survival.