染色质高级结构与肿瘤转移

Chromatin architecture and cancer metastasis

染色质高级结构与基因的转录密切相关,但是,关于染色质高级结构的功能以及染色质高级结构如何促进肿瘤的恶性转变仍然是一个悬而未决的科学问题。在国家自然科学基金"细胞编程与重编程的表观遗传机制"重大研究计划项目支持下,刘喆实验室研究了染色质高级结构在基因转录调控和肿瘤转移中的作用及机制,取得了一系列原创性成果:发现了染色质高级结构在多启动子基因不同启动子活性控制中的重要调控作用,发现在实体肿瘤发生发展过程中染色质高级结构发生了显著变化,并以染色质高级结构的变化为着眼点,发现了淋巴细胞特异性的转录调控系统在实体肿瘤转移中的关键作用,提出了实体肿瘤恶性转变的新的研究方向。现围绕"细胞编程与重编程的表观遗传机制"重大研究计划项目资助下刘喆实验室的原创性工作进行综述。

Increasing evidence has shown that chromatin loops are highly dynamic and tightly correlated with gene function. However, whether these long-range interactions are a cause or consequence of dynamic changes in transcription initiation and how changes of chromatin architecture affect tumorigenesis are still open questions. Supported by the grants from the ＂Epigenetic Mechanisms in Cell Programming and Reprogramming＂ of the Major Research Plan of National Natural Science Foundation of China （NSFC）, we studied the role of chromatin architecture in gene transcription and tumorigenesis. We find that chromatin architecture plays an important role in controlling alternative promoter usage. We also find that significant changes of chromatin higher order organization of adhesion-related genes are accompanied with cancer progression. The underlying mechanism is ectopic expression of lymphocyte restricted transcription factors. These transcription factors reconfigure chromatin architecture of adhesion-related genes, silence their expression, confer cancer cells anchorage independence and promote distal metastasis. Our work links epithelial cancer metastasis with lymphocyte transcriptional program, offering promise for further discoveries to explain mechanisms of lung tumorigenesis. In this article, we summarize our original works funded by the ＂Epigenetic Mechanisms in Cell Programming and Reprogramming＂ of the Major Research Plan of NSFC.