The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression

The 3' lg heavy chain locus (Igh) regulatory region is the most downstream known element of the murine lgh gene cluster. We report here that the nearest non-Igh genes-Crip, Crp2, and Mta1-are located approximate to70 kb further downstream and are beyond the end of the domain of lgh 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.