| Title: |
Relief of a repressed gene expression state in the mouse 1-cell embryo requires DNA replication. |
| Authors: |
Forlani, Sylvie; Bonnerot, Claire; Capgras, Suzanne; Nicolas, Jean Francois Daniel |
| Contributors: |
Biologie moléculaire du développement; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); This work was supported by the Centre National de la Recherche Scientifique (CNRS) and by the Association pour la Recherche sur le Cancer (ARC). J. F. N. and C. B. are from the Institut National de la Recherche Medicale (INSERM).; We thank Nicolas Allen for the gift of TKZ710, TKZ736 and TKZ751 transgenic animals, Laura H. Reid for the gift of plasmids, Joan Shellard for very careful reading of the manuscript and members of our laboratory for discussions. We thank Françoise Kamel for secretarial assistance. |
| Source: |
ISSN: 0950-1991. |
| Publisher Information: |
CCSD; Company of Biologists |
| Publication Year: |
1998 |
| Collection: |
Institut Pasteur: HAL |
| Subject Terms: |
Enhancer; Zygotic gene expression; Transgenic mice; Mouse; Preimplantation embryo; DNA replication; [SDV]Life Sciences [q-bio]; [SDV.BDD]Life Sciences [q-bio]/Development Biology |
| Description: |
International audience ; In the mouse, transcriptional permissiveness is established in the fertilized egg prior to the activation of zygotic genes at the 2-cell stage. Therefore, gene inactivity initiated at the end of gametogenesis results from a complex process, involving more than an inhibition of the basal transcriptional apparatus. We have examined the ability of the first intron (I1) of the human hypoxanthine phosphoribosyl transferase gene, which functions as an enhancer in embryonic stem cells, to activate a reporter gene when placed proximally to or at a distance from the HSV-tk promoter, or when integrated into the mouse genome as part of a stable transgene. In microinjected embryos, I1 functions as an enhancer sequence; however, its competence for long-range activation appears only after the late 1-cell stage and depends on the first DNA replication. Moreover, activation of microinjected transgenes from proximal enhancers occurs in the late 2-cell embryo and in the male pronucleus of 1-cell embryos blocked for DNA replication; whereas, for integrated transgenes, proximal enhancer activity is subject to position effects in the 2-cell embryo and first occurs at the 2- or 4-cell stage, but only after completion of DNA replication. Therefore, the absence of long-range activation and a non-permissive genomic state (the relief of which both depend on DNA replication), together with an inactive transcriptional apparatus, appear to converge to prevent any gene activity in the 1-cell embryo. We propose that the embryo exploits the process of DNA replication to relieve the transcriptionally repressive state that was initially established to fulfil two purposes: (1) to arrest maternal gene expression in the maturing oocyte and (2) to protect the unicellular egg and 1-cell embryo from premature differentiation. Reactivation of gene expression by DNA replication would therefore serve to coordinate cell proliferation and differentiation in the preimplantation embryo. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/9671588; PUBMED: 9671588 |
| Availability: |
https://hal.science/hal-01974102 |
| Accession Number: |
edsbas.DA6778C2 |
| Database: |
BASE |