Department of Immunology, Harvard Medical School, Boston, MA, USA; YCI Laboratory for Immunological Transcriptomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cell. 2019 Feb 7;176(4):897-912.e20. doi: 10.1016/j.cell.2018.12.036. Epub 2019 Jan 24.
A complete chart of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of differentiation and function of an organ system. We generated matched epigenome and transcriptome measurements in 86 primary cell types that span the mouse immune system and its differentiation cascades. This breadth of data enable variance components analysis that suggests that genes fall into two distinct classes, controlled by either enhancer- or promoter-driven logic, and multiple regression that connects genes to the enhancers that regulate them. Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility, pinpointing specific cis-regulatory elements where binding of given TFs is likely functionally relevant, validated by chromatin immunoprecipitation sequencing (ChIP-seq). Overall, this cis-regulatory atlas provides a trove of information on transcriptional regulation through immune differentiation and a foundational scaffold to define key regulatory events throughout the immunological genome.
为了理解器官系统分化和功能的转录基础，我们需要获得顺式调控元件及其动态活性的完整图谱。我们在跨越小鼠免疫系统及其分化级联的 86 种主要细胞类型中生成了匹配的表观基因组和转录组测量结果。这种广泛的数据使方差成分分析成为可能，该分析表明基因分为两类，一类受增强子驱动，另一类受启动子驱动，以及将基因与调控它们的增强子联系起来的多元回归。将转录因子 (TF) 的表达与它们结合基序的全基因组可及性相关联，将它们归类为局部染色质可及性的主要开放或封闭因子，精确定位给定 TF 结合的特定顺式调控元件，这通过染色质免疫沉淀测序 (ChIP-seq) 得到验证。总的来说，这个顺式调控图谱提供了通过免疫分化进行转录调控的大量信息，并为定义整个免疫基因组中的关键调控事件提供了基础框架。
