Replication timing of the chicken lysozyme gene domain Final scientific report

In mammals, there is a clearcut correlation between gene expression and replication timing; active sequences undergo DNA replication early in S phase, while repressed genes are late replicating. In order to investigate how widespread this mechanism may be, we have studied replication timing in the chicken. Our results indicate that two different tissue specific genes, lysozyme and #beta# globin, replicate at a fixed time in all cell types both in vitro and in vivo and are thus not subject to developmental regulation. It thus appears that replication timing does not play a major role in gene regulation in chicken cells. Although replication timing has been shown to correlate with transcription in mammals, the mechanism for this process has not yet been elucidated. One possibility is that active transcription complexes are formed immediately following local replication, and the trans acting factors required for this event are only present in early S phase. In order to test this hypothesis we have developed a system for injecting reporter genes into cells at different times during S phase. Our results clearly show that naked DNA exposed to the transcriptional machinery early in S is 3-5 times more active than if the same gene sequence is injected during late S. These experiments clearly indicate that transcription initiation is regulated by cell cycle progression, suggesting that replication timing indeed plays a role in the control of gene expression. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(65,20) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekGerman-Israeli Foundation for Scientific Research and Development (GIF), Oberschleissheim (Germany)DEGerman