Vertebrate HoxB gene expression requires DNA replication.
To study the relationship between DNA replication and transcription in vivo, we investigated Hox gene activation in two vertebrate systems: the embryogenesis of Xenopus and the retinoic acid-induced differentiation of pluripotent mouse P19 cells. We show that the first cell cycles following the mid- blastula transition in Xenopus are necessary and sufficient for HoxB activation, whereas later cell cycles are necessary for the correct expression pattern. In P19 cells, HoxB expression requires proliferation, and the entire locus is activated within one cell cycle. Using synchronous cultures, we found that activation of HoxB genes is colinear within a single cell cycle, occurs during S phase and requires S phase. The HoxB locus replicates early, whereas replication is still required for maximal expression later in S phase. Thus, induction of HoxB genes occurs in a DNA replication-dependent manner and requires only one cell cycle. We propose that S-phase remodelling licenses the locus for transcriptional regulation.
Fisher
Daniel
D
Institute of Human Genetics, CNRS, 141 rue de la Cardonille, 34396 Cedex 05 Montpellier, France.
Méchali
Marcel
M
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004261:DNA Replication; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000378:metabolism*; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010063:Ovum / Q000187:drug effects; D016196:S Phase; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014981:Xenopus / Q000196:embryology / Q000235:genetics
C101121:HOXB1 homeodomain protein; D018398:Homeodomain Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D014212:Tretinoin; D006918:Hydroxyurea