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KMID : 0381120210430040333
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Genes and Genomics
2021 Volume.43 No. 4 p.333 ~ p.342
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Transglutaminase 2 mediates transcriptional regulation through BAF250a polyamination
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Kim Hyo-Jun
Lee Jin-Haeng
Cho Sung-Yup
Jeon Ju-Hong
Kim In-Gyu
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Abstract
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Background: Transglutaminase 2 (TG2) mediates protein modifications by crosslinking or by incorporating polyamine in response to oxidative or DNA-damaging stress, thereby regulating apoptosis, extracellular matrix formation, and inflammation. The regulation of transcriptional activity by TG2-mediated histone serotonylation or by Sp1 crosslinking may also contribute to cellular stress responses.
Objective: In this study, we attempted to identify TG2-interacting proteins to better understand the role of TG2 in transcriptional regulation.
Methods: Using a yeast two-hybrid assay to screen a HeLa cell cDNA library, we found that TG2 bound BAF250a, a core subunit of the cBAF chromatin remodeling complex, through an interaction between the TG2 barrel 1 and BAF250a C-terminal domains.
Results: TG2 was pulled down with a GST-BAF250a C-term fusion protein. Moreover, TG2 and BAF250a were co-fractionated using P11 chromatography, and co-immunoprecipitated. A transamidation reaction showed that TG2 mediated incorporation of polyamine into BAF250a. In glucocorticoid response-element reporter-expressing cells, TG2 overexpression increased the luciferase reporter activity in a transamidation-dependent manner. In addition, a comparison of genome-wide gene expression between wild-type and TG2-deficient primary hepatocytes in response to dexamethasone treatment showed that TG2 further enhanced or suppressed the expression of dexamethasone-regulated genes that were identified by a gene ontology enrichment analysis.
Conclusion: Thus, our results indicate that TG2 regulates transcriptional activity through BAF250a polyamination.
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KEYWORD
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Transglutaminase 2 (TG2), BAF250a, Transamidation, Dexamethasone, Transcriptional activity
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