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Abstract：
The contact inhibition of proliferation (CIP) denotes the cell density-dependent inhibition of growth, and the loss of CIP represents a hallmark of cancer. However, the mechanism by which CIP regulates gene expression remains poorly understood. Chromatin is a highly complex structure consisting of DNA, histones, and trans-acting factors (TAFs). The binding of TAF proteins to specific chromosomal loci regulates gene expression. Therefore, profiling chromatin is crucial for gaining insight into the gene expression mechanism of CIP. In this study, using modified proteomics of TAFs bound to DNA, we identified a protein that shuttles between the nucleus and cytosol in a cell density-dependent manner. We identified TIPARP, PTGES3, CBFB, and SMAD4 as cell density-dependent nucleocytoplasmic shuttling proteins. In low-density cells, these proteins predominantly reside in the nucleus; however, upon reaching high density, they relocate to the cytosol. Given their established roles in gene regulation, our findings propose their involvement as CIP-dependent TAFs. We also identified and characterized potential open chromatin regions sensitive to changes in cell density. These findings provide insights into the modulation of chromatin structure by CIP.
摘要：
接触抑制增殖（CIP）表示细胞密度依赖性的生长抑制，CIP的丢失代表了癌症的标志。然而,CIP调节基因表达的机制仍知之甚少。染色质是由DNA组成的高度复杂的结构，组蛋白,和反式作用因子(TAF)。TAF蛋白与特定染色体基因座的结合调节基因表达。因此,染色质谱分析对于深入了解CIP的基因表达机制至关重要。在这项研究中,使用与DNA结合的TAFs的改良蛋白质组学，我们发现了一种蛋白质，以细胞密度依赖的方式在细胞核和细胞质之间穿梭。我们确认了TIPARP,PTGES3,CBFB,和SMAD4作为细胞密度依赖性核质穿梭蛋白。在低密度细胞中，这些蛋白质主要存在于细胞核中；然而，一旦达到高密度，他们重新定位到细胞质。鉴于它们在基因调控中的作用，我们的研究结果表明他们参与CIP依赖性TAF。我们还鉴定并表征了对细胞密度变化敏感的潜在开放染色质区域。这些发现为CIP调节染色质结构提供了见解。
