caa a22 4500 397574843 CHVBK 20180308164852.0 cr unu---uuuuu 161202e199609 xx s 000 0 eng 10.1093/hmg/5.9.1345 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.9.1345 Role of Late Replication Timing in the Silencing of X-Linked Genes [Elektronische Daten] [R. Scott Hansen, Theresa K. Canfield, Alan D. Fjeld, Stanley M. Gartler] Cytosine methylation at promoter regions and late replication timing have both been implicated in the regulation of genes subject to X chromosome inactivation. Reported here are studies of X-linked gene replication in normal male and female cells as well as in cell hybrids that contain either a normal active X, a normal inactive X, or an inactive X chromosome that has been treated with the demethylating agent, 5-azacytidine (5aC). The relationship between replication timing and transcriptional activity was examined for XIST, XPCT, PGK1, HPRT, F9, FMR1, IDS, and G6PD, and earlier replication was generally found to be associated with increased transcriptional activity. The HPRT and G6PD genes in an untreated inactive X hybrid were among the few exceptions to this correlation in that they remain inactive, yet replicate earlier than their inactive X alleles present in normal human diploid cells. This condition of earlier replication timing may contribute to the high rates of 5aC-induced reactivation forHPRTand G6PDin this hybrid relative to other inactive X hybrids. Other anomalous cases include 5aC-induced advances in replication time for genes such as XIST and F9 whose transcription was unaltered by treatment. These and other data support a model for regulation of X-inactivated genes that involves at least two levels of control: (i) large chromosomal domains are placed into a transcriptionally nonpermissive state by late replication and (ii) transcription is blocked at the local level by promoter methylation. In addition, our observations of continued XIST expression in 5aC-treated hybrids with reactivated genes indicates that such expression is not sufficient for the maintenance of X inactivation. © 1996 Oxford University Press Hansen R. Scott Department of Medicine, University of Washington, Seattle, WA 98195, USA aut Canfield Theresa K. Department of Medicine, University of Washington, Seattle, WA 98195, USA aut Fjeld Alan D. Department of Medicine, University of Washington, Seattle, WA 98195, USA aut Gartler Stanley M. Department of Medicine, University of Washington, Seattle, WA 98195, USA aut Human Molecular Genetics Oxford University Press 5/9(1996-09), 1345-1353 0964-6906 5:9<1345 1996 5 hmg https://doi.org/10.1093/hmg/5.9.1345 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.9.1345 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hansen R. Scott Department of Medicine, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Canfield Theresa K. Department of Medicine, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Fjeld Alan D. Department of Medicine, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Gartler Stanley M. Department of Medicine, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/9(1996-09), 1345-1353 0964-6906 5:9<1345 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford