Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Sci Adv. 2019 Mar 6;5(3):eaav2448. doi: 10.1126/sciadv.aav2448. eCollection 2019 Mar.
Profiling the chromatin-bound proteome (chromatome) in a simple, direct, and reliable manner might be key to uncovering the role of yet uncharacterized chromatin factors in physiology and disease. Here, we have designed an experimental strategy to survey the chromatome of proliferating cells by using the DNA-mediated chromatin pull-down (Dm-ChP) technology. Our approach provides a global view of cellular chromatome under normal physiological conditions and enables the identification of chromatin-bound proteins de novo. Integrating Dm-ChP with genomic and functional data, we have discovered an unexpected chromatin function for adenosylhomocysteinase, a major one-carbon pathway metabolic enzyme, in gene activation. Our study reveals a new regulatory axis between the metabolic state of pluripotent cells, ribosomal protein production, and cell division during the early phase of embryo development, in which the metabolic flux of methylation reactions is favored in a local milieu.
以简单、直接和可靠的方式描绘染色质结合蛋白质组（chromatome），可能是揭示生理和疾病中尚未表征的染色质因子作用的关键。在这里，我们设计了一种实验策略，通过使用 DNA 介导的染色质下拉（Dm-ChP）技术来检测增殖细胞的染色质组。我们的方法提供了在正常生理条件下细胞染色质组的全局视图，并能够从头鉴定染色质结合蛋白。将 Dm-ChP 与基因组和功能数据整合，我们发现了腺苷同型半胱氨酸酶（一种重要的一碳代谢途径代谢酶）在基因激活中的意想不到的染色质功能。我们的研究揭示了胚胎发育早期多能细胞的代谢状态、核糖体蛋白生成和细胞分裂之间的新调控轴，其中甲基化反应的代谢通量在局部环境中受到青睐。
