The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression.
The 3' Ig heavy chain locus (Igh) regulatory region is the most downstream known element of the murine Igh gene cluster. We report here that the nearest non-Igh genes-Crip, Crp2, and Mta1-are located approximately 70 kb further downstream and are beyond the end of the domain of Igh transcriptional regulation. We have localized an origin of replication in MEL cells to a 3-kb segment located between the 3' Igh regulatory region and Crip. Sequences downstream of this origin are replicated by forks that move in both directions. Sequences upstream of this origin (Igh-C, -D, and -J) are replicated in a single direction through a 500-kb segment in which no active bidirectional origins can be detected. We propose that this origin may lie at or near the end of the Igh regulation domain.
Zhou
Jie
J
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ashouian
Nasrin
N
Delepine
Marc
M
Matsuda
Fumihiko
F
Chevillard
Christophe
C
Riblet
Roy
R
Schildkraut
Carl L
CL
Birshtein
Barbara K
BK
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D006655:Histone Deacetylases; D007070:Immunoglobulin A / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D060588:LIM Domain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D011506:Proteins / Q000235:genetics; D018741:Replication Origin; D012093:Replicon / Q000235:genetics*; D012097:Repressor Proteins; D015534:Trans-Activators
D022782:CCAAT-Enhancer-Binding Protein-beta; C486181:CRIP1 protein, human; D002352:Carrier Proteins; C489507:Crip1 protein, mouse; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D060588:LIM Domain Proteins; C089320:MTA1 protein, human; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases