| First Author | Ji L | Year | 2020 |
| Journal | Biochim Biophys Acta Gene Regul Mech | Volume | 1863 |
| Issue | 5 | Pages | 194518 |
| PubMed ID | 32113985 | Mgi Jnum | J:294118 |
| Mgi Id | MGI:6448201 | Doi | 10.1016/j.bbagrm.2020.194518 |
| Citation | Ji L, et al. (2020) TOPORS, a tumor suppressor protein, contributes to the maintenance of higher-order chromatin architecture. Biochim Biophys Acta Gene Regul Mech 1863(5):194518 |
| abstractText | In the nucleus, chromosomes are hierarchically folded into active (A) and inactive (B) compartments composed of topologically associating domains (TADs). Genomic regions interact with nuclear lamina, termed lamina-associated domains (LADs). However, the molecular mechanisms underlying these 3D chromatin architectures remain incompletely understood. Here, we investigated the role of a potential tumor suppressor, TOP1 Binding Arginine/Serine Rich Protein (TOPORS), in genome organization. In mouse hepatocytes, chromatin interactions between A and B compartments increase and compartmentalization strength is reduced significantly upon Topors knockdown. Correspondingly, strength of TAD boundaries located at A/B borders is weakened. In the absence of TOPORS, chromatin-lamina interactions decrease and the coverage of LADs reduces from 53.31% to 46.52%. Interestingly, these changes in 3D genome are associated with PML nuclear bodies and PML-associated domains (PADs). Moreover, chromatin accessibility is altered predominantly at intergenic regions upon Topors knockdown, including a subset of enhancers. These alterations of chromatin are concordant with transcriptome changes, which are associated with carcinogenesis. Collectively, our findings demonstrate that TOPORS functions as a regulator in chromatin structure, providing novel insight into the architectural roles of tumor suppressors in higher-order genome organization. |
