BRD1-Mediated Acetylation Promotes Integrin αV Gene Expression Via Interaction with Sulfatide
| Autor: | Yi Wei Dong, Rong Wang, Xing Zhong Wu, Zhong Yi Chen, Xiao-Ting Shao, Bao Mei He, Qian Qian Cai, Bing Qi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Models Molecular Cancer Research Carcinoma Hepatocellular Integrin 03 medical and health sciences Cell Line Tumor Humans Histone Chaperones Neoplasm Metastasis ORC1 Molecular Biology Histone Acetyltransferases Regulation of gene expression Gene knockdown Sulfoglycosphingolipids biology Chemistry Liver Neoplasms Nuclear Proteins Acetylation Integrin alphaV Prognosis Survival Analysis Bromodomain Up-Regulation Gene Expression Regulation Neoplastic Histone acetyltransferase binding 030104 developmental biology Histone Oncology Tissue Array Analysis Cancer research biology.protein Female |
| Zdroj: | Molecular cancer research : MCR. 16(4) |
| ISSN: | 1557-3125 |
| Popis: | Integrin αV gene expression is often dysregulated in cancers especially in hepatocellular carcinoma (HCC); however, the mechanism of regulation is poorly understood. Here, it is demonstrated that sulfatide activated integrin αV gene transcription, through histone H3K9/14 acetylation at the promoter, and high integrin αV expression are closely associated with poor prognosis. To elucidate the mechanism of regulation of acetylation, sulfatide-bound proteins were screened by mass spectrometry (MS), and bromodomain containing protein 1 (BRD1) was identified as an interacting protein that also colocalized with sulfatide in HCC cells. BRD1 was also formed a complex with Sp1, which was recruited to the integrin αV gene promoter. Sulfatide was also found to induce BRD1, monocytic leukemia zinc finger (MOZ) and histone acetyltransferase binding to ORC1 (HBO1) acetyltransferase multiprotein complex recruitment to the integrin αV promoter, which is responsible for histone H3K9/14 acetylation. Finally, knockdown of BRD1 limited sulfatide-induced H3K9/14 acetylation and occupancy of MOZ or HBO1 on integrin αV gene promoter. Implications: This study demonstrates that sulfatide interaction with BRD1 mediates acetylation and is important for regulation of integrin αV gene expression. Mol Cancer Res; 16(4); 610–22. ©2018 AACR. |
| Databáze: | OpenAIRE |
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