Reprogramming of DNA replication timing.
Replication timing is an important developmentally regulated regional property that is correlated with chromosome structure and gene expression, but little is known about the establishment and maintenance of these patterns. Here we followed the fate of replication timing patterns in cells that undergo reprogramming either through somatic-cell nuclear transplantation or by the generation of induced pluripotential stem cells. We have investigated three different paradigms, stage-specific replication timing, parental allele-specific asynchrony (imprinted regions), and random allelic asynchronous replication. In all cases, somatic replication timing patterns were reset exactly at the appropriate stage in early development and could be properly established upon re-differentiation. Taken together, these results suggest that, unlike DNA methylation, the molecular mechanisms governing replication timing are not only stable but can also be easily reprogrammed.
Shufaro
Yoel
Y
The Hadassah Human Embryonic Stem Cells Research Center, Goldyne-Savad Institute of Gene Therapy, Department of OB & GYN, Hadassah University Hospital, Jerusalem 91120, Israel.
Lacham-Kaplan
Orly
O
Tzuberi
Ben-Zion
BZ
McLaughlin
John
J
Trounson
Alan
A
Cedar
Howard
H
Reubinoff
Benjamin E
BE
D000483:Alleles; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D002874:Chromosome Mapping; D004261:DNA Replication / Q000235:genetics*; D042522:DNA Replication Timing / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D053652:Nuclear Transfer Techniques; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D015533:Transcriptional Activation