染色质
生物
增强子
遗传学
发起人
转录因子
DNA足迹
Cis监管模块
芯片排序
抄写(语言学)
计算生物学
支架/基质附着区域
嘉雅宠物
基因组
先锋因素
转录协同调节子
核小体
RNA聚合酶Ⅱ
DNA
基因
染色质重塑
DNA结合蛋白
基因表达
哲学
语言学
作者
Samuel H. Kim,Georgi K. Marinov,William J. Greenleaf
出处
期刊:Genome Research
[Cold Spring Harbor Laboratory]
日期:2024-11-21
卷期号:: gr.279621.124-gr.279621.124
标识
DOI:10.1101/gr.279621.124
摘要
Gene regulation in most eukaryotes involves two fundamental physical processes -- alterations in the packaging of the genome by nucleosomes, with active cis -regulatory elements (CREs) generally characterized by an open-chromatin configuration, and the activation of transcription. Mapping these physical properties and biochemical activities genome-wide -- through profiling chromatin accessibility and active transcription -- are key tools used to understand the logic and mechanisms of transcription and its regulation. However, the relationship between these two states has until now not been accessible to simultaneous measurement. To address this, we developed KAS-ATAC, a combination of the KAS-seq (Kethoxal-Assisted SsDNA sequencing and ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) methods for mapping single-stranded DNA (and thus active transcription) and chromatin accessibility, respectively, enabling the genome-wide identification of DNA fragments that are simultaneously accessible and contain ssDNA. We use KAS-ATAC to evaluate levels of active transcription over different classes of regulatory elements in the human genome, to estimate the absolute levels of transcribed accessible DNA over CREs, to map the nucleosomal configurations associated with RNA polymerase activities, and to assess transcription factor association with transcribed DNA through transcription factor binding site (TFBS) footprinting. We observe lower levels of transcription over distal enhancers compared to promoters and distinct nucleosomal configurations around transcription initiation sites associated with active transcription. Most TFs associate equally with transcribed and nontranscribed DNA but a few factors specifically do not exhibit footprints over ssDNA-containing fragments. We anticipate KAS-ATAC to continue to derive useful insights into chromatin organization and transcriptional regulation in other contexts in the future.
科研通智能强力驱动
Strongly Powered by AbleSci AI