Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation.
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.
Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Daan
D
Peric-Hupkes
Wouter
W
Meuleman
Ludo
L
Pagie
Sophia W M
SW
Bruggeman
Irina
I
Solovei
Wim
W
Brugman
Stefan
S
Gräf
Paul
P
Flicek
Ron M
RM
Kerkhoven
Maarten
M
van Lohuizen
Marcel
M
Reinders
Lodewyk
L
Wessels
Bas
B
van Steensel
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D045584:Chromosome Positioning; D004330:Drosophila; D053595:Embryonic Stem Cells / Q000166:cytology*; D016678:Genome; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology; D034881:Nuclear Lamina / Q000378:metabolism*