Replication initiation patterns in the beta-globin loci of totipotent and differentiated murine cells: evidence for multiple initiation regions.
The replication initiation pattern of the murine beta-globin locus was analyzed in totipotent embryonic stem cells and in differentiated cell lines. Initiation events in the murine beta-globin locus were detected in a region extending from the embryonic Ey gene to the adult betaminor gene, unlike the restricted initiation observed in the human locus. Totipotent and differentiated cells exhibited similar initiation patterns. Deletion of the region between the adult globin genes did not prevent initiation in the remainder of the locus, suggesting that the potential to initiate DNA replication was not contained exclusively within the primary sequence of the deleted region. In addition, a deletion encompassing the six identified 5' hypersensitive sites in the mouse locus control region had no effect on initiation from within the locus. As this deletion also did not affect the chromatin structure of the locus, we propose that the sequences determining both chromatin structure and replication initiation lie outside the hypersensitive sites removed by the deletion.
Aladjem
Mirit I
MI
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. maladjem@helix.nih.gov
Rodewald
Luo Wei
LW
Lin
Chii Mai
CM
Bowman
Sarah
S
Cimbora
Daniel M
DM
Brody
Linnea L
LL
Epner
Elliot M
EM
Groudine
Mark
M
Wahl
Geoffrey M
GM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004261:DNA Replication; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D051379:Mice; D016196:S Phase; D017384:Sequence Deletion; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D005914:Globins; D004247:DNA