Molecular Maps of the Reorganization of Genome-Nuclear Lamina Interactions during Differentiation

被引:768
作者
Peric-Hupkes, Daan [1 ]
Meuleman, Wouter [1 ,2 ,5 ]
Pagie, Ludo [1 ]
Bruggeman, Sophia W. M. [3 ]
Solovei, Irina [8 ]
Brugman, Wim [4 ]
Graef, Stefan [9 ]
Flicek, Paul [9 ]
Kerkhoven, Ron M. [4 ]
van Lohuizen, Maarten [3 ,6 ,7 ]
Reinders, Marcel [5 ]
Wessels, Lodewyk [2 ,5 ]
van Steensel, Bas [1 ]
机构
[1] Netherlands Canc Inst, Div Gene Regulat, NL-1066 CX Amsterdam, Netherlands
[2] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands
[3] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands
[4] Netherlands Canc Inst, Cent Microarray Facil, NL-1066 CX Amsterdam, Netherlands
[5] Delft Univ Technol, Fac Elect Engn Math & Comp Sci, NL-2628 CD Delft, Netherlands
[6] Ctr Biomed Genet, NL-3584 CG Utrecht, Netherlands
[7] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands
[8] Univ Munich, Dept Biol 2, D-82152 Planegg Martinsried, Germany
[9] European Bioinformat Inst, Hinxton CB10 1SD, England
关键词
EMBRYONIC STEM-CELLS; GENE-REGULATION; RNA-POLYMERASE; PLURIPOTENT; TRANSCRIPTION; METHYLATION; INDUCTION; ORGANIZATION; REPRESSION; LANGUAGE;
D O I
10.1016/j.molcel.2010.03.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The three-dimensional organization of chromosomes within the nucleus and its dynamics during differentiation are largely unknown. To visualize this process in molecular detail, we generated high-resolution maps of genome-nuclear lamina interactions during subsequent differentiation of mouse embryonic stem cells via lineage-committed neural precursor cells into terminally differentiated astrocytes. This reveals that a basal chromosome architecture present in embryonic stem cells is cumulatively altered at hundreds of sites during lineage commitment and subsequent terminal differentiation. This remodeling involves both individual transcription units and multigene regions and affects many genes that determine cellular identity. Often, genes that move away from the lamina are concomitantly activated; many others, however, remain inactive yet become unlocked for activation in a next differentiation step. These results suggest that lamina-genome interactions are widely involved in the control of gene expression programs during lineage commitment and terminal differentiation.
引用
收藏
页码:603 / 613
页数:11
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