Pluto Bioinformatics

GSE134623: TOPORS, a tumor suppressor protein, maintains higher-order chromatin organization in mouse hepatocytes [RNA-seq]

Bulk RNA sequencing

Within mammalian nuclear space, 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), associated with transcriptional repression. However, the molecular mechanisms underlying these 3D chromatin architectures remain undeciphered. Here, we demonstrate the role of a potential tumor suppressor, TOP1 Binding Arginine/Serine Rich Protein (TOPORS), in genome organization. Topors knockdown in mouse hepatocytes results in cell proliferation and migration promotion, as well as arrest in the S phase of the cell cycle. RNA-seq analysis shows that 373 genes are up-regulated, some of which are associated with nuclear structure, and 316 genes exhibit down-regulated, many related to metabolic process. Chromatin accessibility is inclined to alter in the intergenic regions, including enhancers. Chromatin-lamina interactions decrease globally, and the coverage of LADs reduces from 53.31% to 46.52%. Furthermore, Topors knockdown leads to significantly increasing interactions between A and B compartments in cis and in trans. Correspondingly, strength of TAD boundaries located at A/B borders is weakened. Collectively, our data reveal that TOPORS functions as a regulator in chromosome folding, providing novel insights into the architectural role of tumor suppressors in higher-order genome organization. SOURCE: Bo Wen ( - Fudan University

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