Effects of Collective Histone State Dynamics on Epigenetic Landscape and Kinetics of Cell Reprogramming

被引:19
作者
Ashwin, S. S. [1 ]
Sasai, Masaki [1 ]
机构
[1] Nagoya Univ, Dept Computat Sci & Engn, Nagoya, Aichi 4648603, Japan
基金
日本学术振兴会;
关键词
GENE-EXPRESSION; DIFFERENTIATION; CHROMATIN; MEMORY;
D O I
10.1038/srep16746
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
Cell reprogramming is a process of transitions from differentiated to pluripotent cell states via transient intermediate states. Within the epigenetic landscape framework, such a process is regarded as a sequence of transitions among basins on the landscape; therefore, theoretical construction of a model landscape which exhibits experimentally consistent dynamics can provide clues to understanding epigenetic mechanism of reprogramming. We propose a minimal gene-network model of the landscape, in which each gene is regulated by an integrated mechanism of transcription-factor binding/unbinding and the collective chemical modification of histones. We show that the slow collective variation of many histones around each gene locus alters topology of the landscape and significantly affects transition dynamics between basins. Differentiation and reprogramming follow different transition pathways on the calculated landscape, which should be verified experimentally via single-cell pursuit of the reprogramming process. Effects of modulation in collective histone state kinetics on transition dynamics and pathway are examined in search for an efficient protocol of reprogramming.
引用
收藏
页数:12
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共 57 条
[1]   A Polycomb-based switch underlying quantitative epigenetic memory [J].
Angel, Andrew ;
Song, Jie ;
Dean, Caroline ;
Howard, Martin .
NATURE, 2011, 476 (7358) :105-+
[2]   Regulation of chromatin by histone modifications [J].
Bannister, Andrew J. ;
Kouzarides, Tony .
CELL RESEARCH, 2011, 21 (03) :381-395
[3]  
Bertone P., 2015, BIORXIV
[4]   A deterministic map of Waddington's epigenetic landscape for cell fate specification [J].
Bhattacharya, Sudin ;
Zhang, Qiang ;
Andersen, Melvin E. .
BMC SYSTEMS BIOLOGY, 2011, 5
[5]   Transcriptional regulation by histone modifications: towards a theory of chromatin re-organization during stem cell differentiation [J].
Binder, Hans ;
Steiner, Lydia ;
Przybilla, Jens ;
Rohlf, Thimo ;
Prohaska, Sonja ;
Galle, Joerg .
PHYSICAL BIOLOGY, 2013, 10 (02)
[6]   Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells [J].
Brambrink, Tobias ;
Foreman, Ruth ;
Welstead, G. Grant ;
Lengner, Christopher J. ;
Wernig, Marius ;
Suh, Heikyung ;
Jaenisch, Rudolf .
CELL STEM CELL, 2008, 2 (02) :151-159
[7]   Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase [J].
Buganim, Yosef ;
Faddah, Dina A. ;
Cheng, Albert W. ;
Itskovich, Elena ;
Markoulaki, Styliani ;
Ganz, Kibibi ;
Klemm, Sandy L. ;
van Oudenaarden, Alexander ;
Jaenisch, Rudolf .
CELL, 2012, 150 (06) :1209-1222
[8]   Interplay between gene expression noise and regulatory network architecture [J].
Chalancon, Guilhem ;
Ravarani, Charles N. J. ;
Balaji, S. ;
Martinez-Arias, Alfonso ;
Aravind, L. ;
Jothi, Raja ;
Babu, M. Madan .
TRENDS IN GENETICS, 2012, 28 (05) :221-232
[9]   Systematic Search for Recipes to Generate Induced Pluripotent Stem Cells [J].
Chang, Rui ;
Shoemaker, Robert ;
Wang, Wei .
PLOS COMPUTATIONAL BIOLOGY, 2011, 7 (12)
[10]   Single-Molecule Dynamics of Enhanceosome Assembly in Embryonic Stem Cells [J].
Chen, Jiji ;
Zhang, Zhengjian ;
Li, Li ;
Chen, Bi-Chang ;
Revyakin, Andrey ;
Hajj, Bassam ;
Legant, Wesley ;
Dahan, Maxime ;
Lionnet, Timothee ;
Betzig, Eric ;
Tjian, Robert ;
Liu, Zhe .
CELL, 2014, 156 (06) :1274-1285