PMID- 15707583 OWN - NLM STAT- MEDLINE DCOM- 20050404 LR - 20181201 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 304 IP - 1 DP - 2005 Mar 10 TI - Regulation of replication at the R/G chromosomal band boundary and pericentromeric heterochromatin of mammalian cells. PG - 162-74 AB - Mammalian chromosomes consist of multiple replicons; however, in contrast to yeast, the details of this replication process (origin firing, fork progression and termination) relative to specific chromosomal domains remain unclear. Using direct visualization of DNA fibers, here we show that the rate of replication fork movement typically decreases in the early-mid S phase when the replication fork proceeds through the R/G chromosomal band boundary and pericentromeric heterochromatin. To support this, fluorescence in situ hybridization (FISH)-based replication profiles at the human 1q31.1 (R-band)-32.1 (G-band) regions revealed that replication timing switched around at the putative R/G chromosomal band boundary predicted by marked changes in GC content at the sequence level. Thus, the slowdown of replication fork movement is thought to be the general property of the band boundaries separating the functionally different chromosomal domains. By simultaneous visualization of replication fork movement and pericentromeric heterochromatin sequences on DNA fibers, we observed that this region is duplicated by many replication forks, some of which proceed unidirectionally, that originate from clustered replication origins. We showed that histone hyperacetylation is tightly associated with changes in the replication timing of pericentromeric heterochromatin induced by 5-aza-2'-deoxycytidine treatment. These results suggest that, similar to the yeast system, histone modification is involved in controlling the timing of origin firing in mammals. FAU - Takebayashi, Shin-Ichiro AU - Takebayashi S AD - Laboratory of Molecular and Cellular Biology, Faculty of Bioresources, Mie University, Tsu, Mie 514-8507, Japan. s-take@cdb.riken.jp FAU - Sugimura, Kazuto AU - Sugimura K FAU - Saito, Tatsuro AU - Saito T FAU - Sato, Chiyoko AU - Sato C FAU - Fukushima, Yoshiyuki AU - Fukushima Y FAU - Taguchi, Hiroshi AU - Taguchi H FAU - Okumura, Katsuzumi AU - Okumura K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20041124 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Heterochromatin) RN - 0 (Histones) RN - 776B62CQ27 (Decitabine) RN - 9007-49-2 (DNA) RN - M801H13NRU (Azacitidine) SB - IM MH - Animals MH - Azacitidine/*analogs & derivatives/pharmacology MH - Cell Line MH - Centromere/*physiology MH - Chromosome Banding MH - DNA/biosynthesis MH - *DNA Replication MH - Decitabine MH - Female MH - HeLa Cells MH - Heterochromatin/*physiology MH - Histones/metabolism MH - Humans MH - Interphase MH - Mice MH - Mitosis MH - S Phase EDAT- 2005/02/15 09:00 MHDA- 2005/04/05 09:00 CRDT- 2005/02/15 09:00 PHST- 2004/05/23 00:00 [received] PHST- 2004/10/17 00:00 [revised] PHST- 2004/10/27 00:00 [accepted] PHST- 2005/02/15 09:00 [pubmed] PHST- 2005/04/05 09:00 [medline] PHST- 2005/02/15 09:00 [entrez] AID - S0014-4827(04)00655-X [pii] AID - 10.1016/j.yexcr.2004.10.024 [doi] PST - ppublish SO - Exp Cell Res. 2005 Mar 10;304(1):162-74. doi: 10.1016/j.yexcr.2004.10.024. Epub 2004 Nov 24.