The FIRC Institute of Molecular Oncology (IFOM), Milan, Italy.
Evotec International GmbH, Göttingen, Germany.
Commun Biol. 2022 Aug 27;5(1):882. doi: 10.1038/s42003-022-03846-3.
Chromatin metabolism is frequently altered in cancer cells and facilitates cancer development. While cancer cells produce large amounts of histones, the protein component of chromatin packaging, during replication, the potential impact of histone density on cancer biology has not been studied systematically. Here, we show that altered histone density affects global histone acetylation, histone deactylase inhibitor sensitivity and altered mitochondrial proteome composition. We present estimates of nuclear histone densities in 373 cancer cell lines, based on Cancer Cell Line Encyclopedia data, and we show that a known histone regulator, HMGB1, is linked to histone density aberrations in many cancer cell lines. We further identify an E3 ubiquitin ligase interactor, DCAF6, and a mitochondrial respiratory chain assembly factor, CHCHD4, as histone modulators. As systematic characterization of histone density aberrations in cancer cell lines, this study provides approaches and resources to investigate the impact of histone density on cancer biology.
染色质代谢在癌细胞中经常发生改变，促进了癌症的发展。虽然癌细胞在复制过程中会产生大量的组蛋白，即染色质包装的蛋白质成分，但组蛋白密度对癌症生物学的潜在影响尚未得到系统研究。在这里，我们表明改变的组蛋白密度会影响全局组蛋白乙酰化、组蛋白去乙酰化酶抑制剂敏感性和改变的线粒体蛋白质组组成。我们根据癌症细胞系百科全书的数据，提供了 373 种癌细胞系的核组蛋白密度估计值，并表明一种已知的组蛋白调节剂 HMGB1 与许多癌细胞系的组蛋白密度异常有关。我们进一步鉴定出一种 E3 泛素连接酶相互作用因子 DCAF6 和一种线粒体呼吸链组装因子 CHCHD4 作为组蛋白调节剂。作为对癌细胞系中组蛋白密度异常的系统表征，这项研究提供了方法和资源来研究组蛋白密度对癌症生物学的影响。
