Replication initiation from a novel origin identified in the Th2 cytokine cluster locus requires a distant conserved noncoding sequence

The Journal of Immunology : Official Journal of the American Association of Immunologists
Toshiro HayashidaShoichiro Miyatake

Abstract

Lineage commitment of Th cells is associated with the establishment of specific transcriptional programs of cytokines. However, how Th cell differentiation affects the program of DNA replication has not been addressed. To gain insight into interplays between differentiation-induced transcription regulation and initiation of DNA replication, we took advantage of an in vitro differentiation system of naive T cells, in which one can manipulate their differentiation into Th1 or Th2 cells. We searched for replication origins in the murine IL-4/IL-13 locus and compared their profiles in the two Th cell lineages which were derived in vitro from the same precursor T cells. We identified a replication origin (ori(IL-13)) downstream from exon 4 of IL-13 and showed that this origin functions in both Th2 and Th1 cells. A distant regulatory element called CNS-1 (conserved noncoding sequence 1) in the IL-4/IL-13 intergenic region coincides with a Th2-specific DNase I-hypersensitive site and is required for efficient, coordinated expression of Th2 cytokines. Replication initiation from ori(IL-13) is significantly reduced in Th1 and Th2 cells derived from CNS-1-deficient mice. However, the replication timing of this locus is consistently early...Continue Reading

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Citations

Apr 9, 2010·Annual Review of Biochemistry·Hisao MasaiMasako Oda
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kazuhisa AokiShoichiro Miyatake
Sep 3, 2010·The EMBO Journal·Subhradip KarmakarSherman M Weissman
May 12, 2016·Epigenetics & Chromatin·Owen K SmithMirit I Aladjem
Nov 22, 2016·Nature Reviews. Genetics·Mirit I Aladjem, Christophe E Redon
Dec 18, 2013·Chromosoma·Vladimir V SherstyukSuren M Zakian
Aug 5, 2011·Genome Research·Melvenia M MartinMirit I Aladjem
Feb 22, 2012·Biochimica Et Biophysica Acta·Amy L Conner, Mirit I Aladjem

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