Separation of transcriptional repressor and activator functions in Drosophila HDAC3

被引：3

作者：

Tang, Min ^{[1
,2
]}

Regadas, Isabel ^{[1
]}

Belikov, Sergey ^{[1
]}

Shilkova, Olga ^{[1
,3
]}

Xu, Lei ^{[4
,5
]}

Wernersson, Erik ^{[4
]}

Liu, Xuewen ^{[2
]}

Wu, Hongmei ^{[2
]}

Bienko, Magda ^{[4
,5
]}

Mannervik, Mattias ^{[1
]}

机构：

[1] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden

[2] Univ South China, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China

[3] Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden

[4] Karolinska Inst, Dept Med Biochem & Biophys, S-17165 Stockholm, Sweden

[5] Sci Life Lab, S-17165 Stockholm, Sweden

来源：

DEVELOPMENT | 2023年 / 150卷 / 15期

基金：

中国国家自然科学基金;

关键词：

HDAC3; Histone deacetylase; Chromatin; Transcription; Embryo development; Drosophila; HISTONE DEACETYLASE 3; NUCLEAR-ENVELOPE PROTEIN; GENE-EXPRESSION; ACETYLATION; MECHANISM; INTERACTS; DELETION; PROGRAM; DOMAINS; H4;

D O I：

10.1242/dev.201548

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The histone deacetylase HDAC3 is associated with the NCoR/SMRT co-repressor complex, and its canonical function is in transcriptional repression, but it can also activate transcription. Here, we show that the repressor and activator functions of HDAC3 can be genetically separated in Drosophila. A lysine substitution in the N terminus (K26A) disrupts its catalytic activity and activator function, whereas a combination of substitutions (HEBI) abrogating the interaction with SMRTER enhances repressor activity beyond wild type in the early embryo. We conclude that the crucial functions of HDAC3 in embryo development involve catalytic-dependent gene activation and non-enzymatic repression by several mechanisms, including tethering of loci to the nuclear periphery.

引用

页数：12

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