Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin

被引:37
作者
Pownall, Mark E. [1 ]
Miao, Liyun [1 ]
Vejnar, Charles E. [1 ]
M'Saad, Ons [2 ,3 ]
Sherrard, Alice [1 ]
Frederick, Megan A. [4 ]
Benitez, Maria D. J. [1 ]
Boswell, Curtis W. [1 ]
Zaret, Kenneth S. [4 ]
Bewersdorf, Joerg [2 ,3 ,5 ,6 ,7 ]
Giraldez, Antonio J. [1 ,8 ,9 ]
机构
[1] Yale Univ, Dept Genet, Sch Med, New Haven, CT 06510 USA
[2] Yale Univ, Dept Cell Biol, Sch Med, New Haven, CT 06510 USA
[3] Yale Univ, Dept Biomed Engn, New Haven, CT 06510 USA
[4] Univ Penn, Perelman Sch Med, Inst Regenerat Med, Philadelphia, PA 19104 USA
[5] Yale Univ, Kavli Inst Neurosci, Sch Med, New Haven, CT 06510 USA
[6] Yale Univ, Dept Phys, New Haven, CT 06510 USA
[7] Yale Univ, Nanobiol Inst, West Haven, CT 06477 USA
[8] Yale Univ, Yale Stem Cell Ctr, Sch Med, New Haven, CT 06510 USA
[9] Yale Univ, Yale Canc Ctr, Sch Med, New Haven, CT 06510 USA
基金
英国惠康基金; 美国国家卫生研究院;
关键词
RNA-POLYMERASE-II; C-TERMINAL DOMAIN; GENERAL-METHOD; IMAGE-ANALYSIS; IN-VIVO; ACTIVATION; DYNAMICS; NANOG; CELL; FLUOROPHORES;
D O I
10.1126/science.ade5308
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Nanoscale chromatin organization regulates gene expression. Although chromatin is notably reprogrammed during zygotic genome activation (ZGA), the organization of chromatin regulatory factors during this universal process remains unclear. In this work, we developed chromatin expansion microscopy (ChromExM) to visualize chromatin, transcription, and transcription factors in vivo. ChromExM of embryos during ZGA revealed how the pioneer factor Nanog interacts with nucleosomes and RNA polymerase II (Pol II), providing direct visualization of transcriptional elongation as string-like nanostructures. Blocking elongation led to more Pol II particles clustered around Nanog, with Pol II stalled at promoters and Nanog-bound enhancers. This led to a new model termed "kiss and kick", in which enhancer-promoter contacts are transient and released by transcriptional elongation. Our results demonstrate that ChromExM is broadly applicable to study nanoscale nuclear organization.
引用
收藏
页码:92 / 99
页数:8
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