Replication Initiation from a Novel Origin Identified in the Th2 Cytokine Cluster Locus Requires a Distant Conserved Noncoding Sequence
作者： Toshiro Hayashida , Masako Oda , Kanako Ohsawa , Atsumi Yamaguchi , Takumi Hosozawa
DOI: 10.4049/JIMMUNOL.176.9.5446
关键词: Replication timing 、 Licensing factor 、 Origin of replication 、 Control of chromosome duplication 、 Replication factor C 、 Eukaryotic DNA replication 、 Pre-replication complex 、 Genetics 、 Biology 、 Origin recognition complex
摘要: Lineage commitment of Th cells is associated with the establishment specific transcriptional programs cytokines. However, how cell differentiation affects program DNA replication has not been addressed. To gain insight into interplays between differentiation-induced transcription regulation and initiation replication, we took advantage an in vitro system naive T cells, which one can manipulate their Th1 or Th2 cells. We searched for origins murine IL-4/IL-13 locus compared profiles two lineages were derived from same precursor identified a origin (ori(IL-13)) downstream exon 4 IL-13 showed that this functions both A distant regulatory element called CNS-1 (conserved noncoding sequence 1) intergenic region coincides Th2-specific DNase I-hypersensitive site required efficient, coordinated expression Replication ori(IL-13) significantly reduced CNS-1-deficient mice. timing consistently early during S phase under either wild-type deletion background. Thus, conserved regulates manner independent its effect on lineage-specific but segment surrounding origin.
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