Systematic identification of gene family regulators in mouse and human embryonic stem cells.
Systematic identification of gene family regulators in mouse and human embryonic stem cells.
复制标题
小鼠和人类胚胎干细胞中基因家族调节剂的系统鉴定。
DOI：
10.1093/nar/gkw259
复制
发表时间：
2016-05-19
影响因子：
14.9
通讯作者：
Meshorer E
中科院分区：
文献类型：
--
作者：
Aaronson Y;Livyatan I;Gokhman D;Meshorer E
多能自我更新的胚胎干细胞（ESC）已经成为越来越多的高通量实验的焦点，揭示了数百种转录因子和组蛋白修饰的全基因组位置。虽然大多数数据集都用于特定的背景下，但所有数据集的组合提供了染色质特征和控制细胞状态的调控元件的全面视图。在这里，我们使用ESCs中的数百个数据集，生成了染色质蛋白和修饰的共定位图，并建立了基因家族调控蛋白的发现管道。通过将全基因组结合数据与数百个基因的过表达和敲低分析进行比较，我们发现多能性相关因子NR5A2将线粒体基因与细胞溶质核糖体基因分开，调节它们的表达。我们进一步表明，具有共同的染色质谱的基因被富集为不同的基因本体论（GO）类别。我们的方法可以推广到揭示任何基因组的共同调节，发现新的基因家族，并确定共同的基因组元件的基础上共享的染色质特征。
Pluripotent self-renewing embryonic stem cells (ESCs) have been the focus of a growing number of high-throughput experiments, revealing the genome-wide locations of hundreds of transcription factors and histone modifications. While most of these datasets were used in a specific context, all datasets combined offer a comprehensive view of chromatin characteristics and regulatory elements that govern cell states. Here, using hundreds of datasets in ESCs, we generated colocalization maps of chromatin proteins and modifications, and built a discovery pipeline for regulatory proteins of gene families. By comparing genome-wide binding data with over-expression and knockdown analysis of hundreds of genes, we discovered that the pluripotency-related factor NR5A2 separates mitochondrial from cytosolic ribosomal genes, regulating their expression. We further show that genes with a common chromatin profile are enriched for distinct Gene Ontology (GO) categories. Our approach can be generalized to reveal common regulators of any gene group; discover novel gene families, and identify common genomic elements based on shared chromatin features.