The replication timing of CFTR and adjacent genes.
Correlations between transcriptional activity and replication timing have been observed for the human cystic fibrosis transmembrane conductance regulator (CFTR) gene, as well as for other tissue-specific genes. In addition, the patterns of histone modifications and the nuclear positioning of chromosomal loci appear to be related to their replication timing. It is not understood why and how these different features are functionally linked. To address this problem, we investigated the replication timing of the human CFTR gene and of adjacent genes. Recently, we could show that CFTR and adjacent genes associate independently from each other with different nuclear regions and chromatin fractions, in accordance with their individual transcriptional regulation. Together, the results show that not the transcriptional activity, but rather the nuclear position of CFTR and adjacent genes appears to be a major determinant of their replication timing. Furthermore, the results imply a specific functional order of nuclear changes related to switches in replication timing.
Englmann
Andreas
A
Ludwig Maximilians University Munich, Department of Biology II, Grosshaderner Str. 2, 82152, Planegg-Martinsried, Germany.
Clarke
Luka A
LA
Christan
Susanne
S
Amaral
Margarida D
MD
Schindelhauer
Dirk
D
Zink
Daniele
D
D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D014158:Transcription, Genetic
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator