1. Linking nuclear matrix–localized PIAS1 to chromatin SUMOylation via direct binding of histones H3 and H2A.Z
- Author
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Jiwen Li, Jiemin Wong, Wei Wei, Qingqing Guan, Jing Luo, Huifang Zhang, Yunpeng Zhang, Xiang Xu, Jialun Li, Zhaosu Chen, and Lujian Liao
- Subjects
Transcription, Genetic ,SUMO protein ,DSP, dithiobis succinimidyl propionate ,PIAS1 ,Biochemistry ,Histones ,Protein Domains ,Transcription (biology) ,histone SUMOylation ,Humans ,Protein inhibitor of activated STAT ,Molecular Biology ,biology ,co-IP, coimmunoprecipitation ,Chemistry ,SUMO, small ubiquitin-related modifier ,Sumoylation ,Cell Biology ,Nuclear matrix ,Protein Inhibitors of Activated STAT ,Chromatin ,Ubiquitin ligase ,Cell biology ,ChIP, chromatin immunoprecipitation ,HEK293 Cells ,Histone ,SUMO ,nuclear matrix ,Small Ubiquitin-Related Modifier Proteins ,biology.protein ,Function (biology) ,Research Article ,HeLa Cells - Abstract
As a conserved posttranslational modification, SUMOylation has been shown to play important roles in chromatin-related biological processes including transcription. However, how the SUMOylation machinery associates with chromatin is not clear. Here, we present evidence that multiple SUMOylation machinery components, including SUMO E1 proteins SAE1 and SAE2 and the PIAS (protein inhibitor of activated STAT) family SUMO E3 ligases, are primarily associated with the nuclear matrix rather than with chromatin. We show using nuclease digestion that all PIAS family proteins maintain nuclear matrix association in the absence of chromatin. Of importance, we identify multiple histones including H3 and H2A.Z as directly interacting with PIAS1 and demonstrate that this interaction requires the PIAS1 SAP (SAF-A/B, Acinus, and PIAS) domain. We demonstrate that PIAS1 promotes SUMOylation of histones H3 and H2B in both a SAP domain- and an E3 ligase activity-dependent manner. Furthermore, we show that PIAS1 binds to heat shock-induced genes and represses their expression and that this function also requires the SAP domain. Altogether, our study reveals for the first time the nuclear matrix as the compartment most enriched in SUMO E1 and PIAS family E3 ligases. Our finding that PIAS1 interacts directly with histone proteins also suggests a molecular mechanism as to how nuclear matrix-associated PIAS1 is able to regulate transcription and other chromatin-related processes.
- Published
- 2021