Genome accessibility is widely preserved and locally modulated during mitosis.
Chris C.-S. Hsiung,Chris C.-S. Hsiung,Christapher S. Morrissey,Maheshi Udugama,Christopher L. Frank,Cheryl A. Keller,Songjoon Baek,Belinda Giardine,Gregory E. Crawford,Myong-Hee Sung,Ross C. Hardison,Gerd A. Blobel +11 more
TLDR
It is concluded that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements.Abstract:
Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that such mitotically retained molecular signatures could provide transcriptional memory through mitosis. To understand the role of chromatin structure in mitotic memory, we performed the first genome-wide comparison of DNase I sensitivity of chromatin in mitosis and interphase, using a murine erythroblast model. Despite chromosome condensation during mitosis visible by microscopy, the landscape of chromatin accessibility at the macromolecular level is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly DNase hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility more strongly, whereas distal regulatory elements tend to lose accessibility. Large domains of DNA hypomethylation mark a subset of promoters that retain accessibility during mitosis and across many cell types in interphase. Erythroid transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but has little influence on mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements.read more
Citations
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ChromHMM: automating chromatin-state discovery and characterization
TL;DR: ChromHMM is developed, an automated computational system for learning chromatin states, characterizing their biological functions and correlations with large-scale functional datasets, and visualizing the resulting genome-wide maps of chromatin state annotations.
Journal ArticleDOI
A dynamic mode of mitotic bookmarking by transcription factors
TL;DR: It is reported that many TFs remain associated with chromosomes in mouse embryonic stem cells, and that the exclusion previously described is largely a fixation artifact.
Journal ArticleDOI
Mitotic transcription and waves of gene reactivation during mitotic exit
Katherine C. Palozola,Greg Donahue,Hong Liu,Gregory R. Grant,Justin S. Becker,Allison Cote,Hongtao Yu,Arjun Raj,Kenneth S. Zaret +8 more
TL;DR: It is proposed that the cell’s transcription pattern is largely retained at a low level through mitosis, whereas the amplitude of transcription observed in interphase is reestablished during mitotic exit.
Journal ArticleDOI
Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming.
Abdenour Soufi,Stephen Dalton +1 more
TL;DR: How cell fate decisions in development are linked to the cell cycle, and the key molecular components thereof are discussed.
Journal ArticleDOI
Establishment and maintenance of heritable chromatin structure during early Drosophila embryogenesis.
Shelby A. Blythe,Eric Wieschaus +1 more
TL;DR: It is found that regions of accessibility are established sequentially, where enhancers are opened in advance of promoters and insulators, and stably maintained in highly condensed mitotic chromatin to ensure faithful inheritance of prior accessibility status across cell divisions.
References
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Robert E. Thurman,Eric Rynes,Richard Humbert,Jeff Vierstra,Matthew T. Maurano,Eric Haugen,Nathan C. Sheffield,Andrew B. Stergachis,Hao Wang,Benjamin Vernot,Kavita Garg,Sam John,Richard Sandstrom,Daniel Bates,Lisa Boatman,Theresa K. Canfield,Morgan Diegel,Douglas Dunn,Abigail K. Ebersol,Tristan Frum,Erika Giste,Audra K. Johnson,Ericka M. Johnson,Tanya Kutyavin,Bryan R. Lajoie,Bum Kyu Lee,Kristen Lee,Darin London,Dimitra Lotakis,Shane Neph,Fidencio Neri,Eric D. Nguyen,Hongzhu Qu,Hongzhu Qu,Alex Reynolds,Vaughn Roach,Alexias Safi,Minerva E. Sanchez,Amartya Sanyal,Anthony Shafer,Jeremy M. Simon,Lingyun Song,Shinny Vong,Molly Weaver,Yongqi Yan,Zhancheng Zhang,Zhuzhu Zhang,Boris Lenhard,Muneesh Tewari,Michael O. Dorschner,R. Scott Hansen,Patrick A. Navas,George Stamatoyannopoulos,Vishwanath R. Iyer,Jason D. Lieb,Shamil R. Sunyaev,Joshua M. Akey,Peter J. Sabo,Rajinder Kaul,Terrence S. Furey,Job Dekker,Gregory E. Crawford,John A. Stamatoyannopoulos,John A. Stamatoyannopoulos +63 more
TL;DR: The first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types is presented, revealing novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.
Journal ArticleDOI
ChromHMM: automating chromatin-state discovery and characterization
TL;DR: ChromHMM as mentioned in this paper is an automated computational system for learning chromatin states, characterizing their biological functions and correlations with large-scale functional datasets, and visualizing the resulting genome-wide maps of chromatin state annotations.