ARID1A deficiency weakens BRG1-RAD21 interaction that jeopardizes chromatin compactness and drives HCC metastasis

ARID1A, encoding a subunit of SWI/SNF chromatin remodeling complex, is widely recognized as a tumor suppressor gene in multiple tumor types including hepatocellular carcinoma (HCC). Previous studies have demonstrated that ARID1A deficiency can cause HCC metastasis, possibly due to the altered chromatin organization, however the underlying mechanisms of which remain poorly understood. To address the effect of Arid1a deficiency on chromatin organization, we generated high resolution chromatin interaction matrices, and exploited the conformation changes upon Arid1a depletion in mouse hepatocytes.

ARID1A 编码SWI/SNF染色质重塑复合物（SWI/SNF chromatin remodeling complex）的一个亚基，现已被广泛认定为包括肝细胞癌（hepatocellular carcinoma, HCC）在内的多种肿瘤类型中的抑癌基因。既往研究表明，ARID1A缺失可促进肝细胞癌转移，其潜在机制可能与染色质组织改变相关，但目前该过程的具体分子机制仍不甚明晰。为阐明ARID1A缺失对染色质组织的影响，本研究构建了高分辨率染色质相互作用矩阵，并分析了小鼠肝细胞中ARID1A敲除后的染色质构象变化。