期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 22, 期 13, 页码 4876-4889出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.22.13.4876-4889.2002
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资金
- NCI NIH HHS [P30CA13330, P30 CA013330] Funding Source: Medline
- NIAID NIH HHS [R01 AI013509, R01 AI023548, R37 AI013509, AI23548, AI13509] Funding Source: Medline
- NIGMS NIH HHS [GM45751, R01 GM045751] Funding Source: Medline
The murine immunoglobulin heavy-chain (Igh) locus provides an important model for understanding the replication of tissue-specific gene loci in mammalian cells. We have observed two DNA replication programs with dramatically different temporal replication patterns for the Igh locus in B-lineage cells. In pro- and pre-B-cell lines and in ex vivo-expanded pro-B cells, the entire locus is replicated early in S phase. In three cell lines that exhibit the early-replication pattern, we found that replication forks progress in both directions through the constant-region genes, which is consistent with the activation of multiple initiation sites. In contrast, in plasma cell lines, replication of the Igh locus occurs through a triphasic pattern similar to that previously detected in MEL cells. Sequences downstream of the Igh-Calpha gene replicate early in S, while heavy-chain variable (Vh) gene sequences replicate late in S. An similar to500-kb transition region connecting sequences that replicate early and late is replicated progressively later in S. The formation of the transition region in different cell lines is independent of the sequences encompassed. In B-cell lines that exhibit a triphasic-replication pattern, replication forks progress in one direction through the examined constant-region genes. Timing data and the direction of replication fork movement indicate that replication of the transition region occurs by a single replication fork, as previously described for MEL cells. Associated with the contrasting replication programs are differences in the subnuclear locations of Igh loci. When the entire locus is replicated early in S, the Igh locus is located away from the nuclear periphery, but when Vh gene sequences replicate late and there is a temporal-transition region, the entire Igh locus is located near the nuclear periphery.
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