{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:47:01Z","timestamp":1770983221089,"version":"3.50.1"},"reference-count":34,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5382","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1998,9,4]]},"abstract":"<jats:p>Microscopy shows that individual sites of DNA replication and transcription of mammalian nuclei segregate into sets of roughly 22 and 16 higher order domains, respectively. Each domain set displayed a distinct network-like appearance, including regions of individual domains and interdigitation of domains between the two networks. These data support a dynamic mosaic model for the higher order arrangement of genomic function inside the cell nuclei.<\/jats:p>","DOI":"10.1126\/science.281.5382.1502","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:49:42Z","timestamp":1027763382000},"page":"1502-1505","source":"Crossref","is-referenced-by-count":205,"title":["Segregation of Transcription and Replication Sites Into Higher Order Domains"],"prefix":"10.1126","volume":"281","author":[{"given":"Xiangyun","family":"Wei","sequence":"first","affiliation":[{"name":"X. Wei, J. Samarabandu, A. J. Siegel, R. Berezney, Departments of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA. R. S. Devdhar and R. Acharya, Department of Electrical and Computer Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jagath","family":"Samarabandu","sequence":"additional","affiliation":[{"name":"X. Wei, J. Samarabandu, A. J. Siegel, R. Berezney, Departments of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA. R. S. Devdhar and R. Acharya, Department of Electrical and Computer Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakendu S.","family":"Devdhar","sequence":"additional","affiliation":[{"name":"X. Wei, J. Samarabandu, A. J. Siegel, R. Berezney, Departments of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA. R. S. Devdhar and R. Acharya, Department of Electrical and Computer Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan J.","family":"Siegel","sequence":"additional","affiliation":[{"name":"X. Wei, J. Samarabandu, A. J. Siegel, R. Berezney, Departments of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA. R. S. Devdhar and R. Acharya, Department of Electrical and Computer Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj","family":"Acharya","sequence":"additional","affiliation":[{"name":"X. Wei, J. Samarabandu, A. J. Siegel, R. Berezney, Departments of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA. R. S. Devdhar and R. 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Cytol. vols. 162 A and B (Academic Press New York 1995)]."},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev.cb.09.110193.001405","volume":"9","author":"Spector D. L.","year":"1993","unstructured":"Spector D. L., Annu. Rev. Cell Biol. 9, 265 (1993);","journal-title":"Annu. Rev. Cell Biol."},{"key":"e_1_3_1_3_3","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1126\/science.8446901","volume":"259","author":"Xing Y.","year":"1993","unstructured":"Xing Y., Johnson C. V., Dobner P. R., Lawrence J. B., Science 259, 1326 (1993);","journal-title":"Science"},{"key":"e_1_3_1_3_4","unstructured":"; M. Hoffman ibid. p. 1257; Y. Baskin ibid. 268 1564 (1995)."},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1242\/jcs.26.1.281","volume":"26","author":"Stack S. M.","year":"1977","unstructured":"Stack S. M., Brown D. B., Dewey W. C., J. Cell Sci. 26, 281 (1977);","journal-title":"J. Cell Sci."},{"key":"e_1_3_1_4_3","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1101\/SQB.1993.058.01.085","volume":"58","author":"Cremer T.","year":"1993","unstructured":"Cremer T., et al., Cold Spring Harbor Symp. Quant. Biol. 58, 777 (1993).","journal-title":"Cold Spring Harbor Symp. Quant. Biol."},{"key":"e_1_3_1_5_2","unstructured":"R. Berezney in Chromosomal Non-Histone Proteins L. S. Hnilica Ed. (CRC Press Boca Raton FL 1984) vol. 4 pp. 119\u2013180."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1083\/jcb.108.1.1","volume":"108","author":"Nakayasu H.","year":"1989","unstructured":"Nakayasu H., Berezney R., J. Cell Biol. 108, 1 (1989).","journal-title":"J. Cell Biol."},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/j.1460-2075.1993.tb05747.x","volume":"12","author":"Jackson D. A.","year":"1993","unstructured":"Jackson D. A., Hassan A. B., Errington R. J., Cook P. R., EMBO J. 12, 1059 (1993).","journal-title":"EMBO J."},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/BF00229430","volume":"70","author":"Smith H. C.","year":"1986","unstructured":"Smith H. C., Ochs R. L., Fernandez E. A., Spector D. L., Mol. Cell. Biochem. 70, 151 (1986);","journal-title":"Mol. Cell. Biochem."},{"key":"e_1_3_1_8_3","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1083\/jcb.112.6.1055","volume":"112","author":"Xing Y.","year":"1991","unstructured":"Xing Y., Lawrence J. B., J. Cell Biol. 112, 1055 (1991).","journal-title":"J. Cell Biol."},{"key":"e_1_3_1_9_2","unstructured":"Labeling of DNA and RNA synthesis sites which was performed based on previously published methods and drug inhibition experiments indicates that extranucleolar transcription sites visualized with this procedure are predominantly if not exclusively mediated by RNA polymerase II [(5 6);"},{"key":"e_1_3_1_9_3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1083\/jcb.122.2.283","volume":"122","author":"Wansink D. G.","year":"1993","unstructured":"Wansink D. G., et al., J. Cell Biol. 122, 283 (1993);","journal-title":"J. Cell Biol."},{"key":"e_1_3_1_9_4","unstructured":"]. Cells permeabilized with 0.025% Triton X-100 were immediately incubated with nuclei acid synthesis buffer [50 mM tris-HCl (pH 7.4) 10 mM MgCl 2 150 mM NaCl 25% glycerol 0.5 mM phenylmethylsulfonyl fluoride RNasin (25 U\/ml) 1.8 mM ATP 0.5 mM CTP GTP BrUTP 0.1 mM dATP 0.1 mM dCTP 0.1 mM dGTP and 25 \u03bcM digoxigenin-11-dUTP] at room temperature for 30 min to label transcription sites and replication sites simultaneously then were fixed in 100% methanol at \u201320\u00b0C for 20 min followed by 3% paraformaldehyde in phosphate-buffered saline on ice for 5 min."},{"key":"e_1_3_1_10_2","unstructured":"For labeling RNA sites rat monoclonal antibody to BrdU (Sera-Lab) was used followed by biotin-conjugated goat anti-rat immunoglobulin G and Texas red\u2013conjugated stepavidin incubation. Fluorescein isothiocyanate (FITC)\u2013 conjugated sheep anti-digoxigenin Fab fragments (Boehringer Mannheim) were used for labeling DNA sites. Images from 0.5-\u03bcm optical sections were collected with a Bio-Rad MRC-1024 confocal microscope equipped with a krypton argon laser to excite FITC and Texas red simultaneously at 488-nm and 568-nm wavelength respectively."},{"key":"e_1_3_1_11_2","unstructured":"DNA replication is temporally controlled in the S phase with transcriptionally active genes usually replicated in early S phase and nonactive genes in late S phase ["},{"key":"e_1_3_1_11_3","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1126\/science.6719109","volume":"224","author":"Goldman M. A.","year":"1984","unstructured":"Goldman M. A., Holmquist G. P., Gray M. C., Caston L. A., Nag A., Science 224, 686 (1984);","journal-title":"Science"},{"key":"e_1_3_1_11_4","first-page":"2149","volume":"8","author":"Hatton K. A.","year":"1988","unstructured":"Hatton K. A., et al., Mol. Cell. Biol. 8, 2149 (1988);","journal-title":"Mol. Cell. Biol."},{"key":"e_1_3_1_11_5","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1002\/j.1460-2075.1992.tb05162.x","volume":"11","author":"Selig S.","year":"1992","unstructured":"Selig S., Okumura K., Ward D. C., Cedar H., EMBO J. 11, 1217 (1992);","journal-title":"EMBO J."},{"key":"e_1_3_1_11_6","unstructured":"]. Also DNA replication sites show different patterns in different periods of S phase (5)."},{"key":"e_1_3_1_12_2","unstructured":"Visual comparison of replication sites and transcription sites was used to determine the number of replication sites that are colocalized with transcription sites. The total numbers of replication and transcription sites were calculated using a segmentation algorithm specifically developed in our laboratory for three-dimensional confocal images ["},{"key":"e_1_3_1_12_3","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1117\/12.208708","volume":"2434","author":"Samarabandu J.","year":"1995","unstructured":"Samarabandu J., Ma H., Acharya R., Cheng P. C., Berezney R., Proc. SPIE 2434, 370 (1995)].","journal-title":"Proc. SPIE"},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1242\/jcs.107.6.1449","volume":"107","author":"Wansink D. G.","year":"1994","unstructured":"Wansink D. G., et al., J. Cell Sci. 107, 1449 (1994).","journal-title":"J. Cell Sci."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1242\/jcs.107.2.425","volume":"107","author":"Hassan A. B.","year":"1994","unstructured":"Hassan A. B., Errington R., White N., Jackson D., Cook P., J. Cell Sci. 107, 425 (1994).","journal-title":"J. Cell Sci."},{"key":"e_1_3_1_15_2","unstructured":"Using Microsoft Power Point nuclear regions with three or more sites of one and only one activity were contoured as preferential cluster regions. Regions with mixed distribution patterns of replication and transcription sites were displayed as yellow. The relative sizes of the corresponding areas were directly measured."},{"key":"e_1_3_1_16_2","unstructured":"If we include nucleolar regions in the transcription cluster category the area occupied by clustered replication and transcription sites will increase to about 80% of the total contoured areas."},{"key":"e_1_3_1_17_2","unstructured":"Synchronization was achieved by serum deprivation followed by aphidicolin inhibition at the G 1 \/S border ["},{"key":"e_1_3_1_17_3","first-page":"1108","volume":"35","author":"Spadari S.","year":"1985","unstructured":"Spadari S., et al., Drug Res. 35, 1108 (1985);","journal-title":"Drug Res."},{"key":"e_1_3_1_17_4","unstructured":"]. Contour analysis on 3T3 mouse cells synchronized at the G 1 \/S border showed that 64% of the contoured area is occupied by replication and transcription site clusters."},{"key":"e_1_3_1_18_2","unstructured":"Cluster analysis was performed on \u201cSn\u201d number of clusters that were generated using the \u201crandom ( )\u201d library function. Of the total number of sites some were randomly chosen to be transcription sites (red) and the remaining were marked as replication sites (green). Computation of radii of clusters is based on a Gaussian distribution function with a standard deviation of 1.7."},{"key":"e_1_3_1_19_2","unstructured":"Three-dimensional reconstruction of the contours was performed from the confocal optical sections using the drawing tool of IPlab (Signal Analytics)."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"6746","DOI":"10.1073\/pnas.94.13.6746","volume":"94","author":"Zeng C.","year":"1997","unstructured":"Zeng C., et al., Proc. Natl. Acad. Sci. U.S.A. 94, 6746 (1997);","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_20_3","first-page":"1585","volume":"95","author":"Zeng C.","year":"1998","unstructured":"Zeng C., et al., ibid. 95, 1585 (1998).","journal-title":"ibid."},{"key":"e_1_3_1_21_2","unstructured":"R. Summers and A. Stonebraker (Confocal Microscopy and 3D Imaging Facility of the School of Medicine and Biomedical Sciences SUNY at Buffalo) provided valuable assistance with confocal microscopy. Computer image analysis was performed at the Microscopic Imaging Facility (Department of Biological Sciences SUNY at Buffalo). NHF- 1 normal human fibroblast cells were kindly provided by D. G. Kaufman University of North Carolina School of Medicine. Supported by NIH grant GM 23922 (R.B.) and a Mark Diamond Graduate Student Research Grant from SUNY at Buffalo (X.W.) (45F97)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.281.5382.1502","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T05:10:47Z","timestamp":1705122647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.281.5382.1502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,9,4]]},"references-count":34,"journal-issue":{"issue":"5382","published-print":{"date-parts":[[1998,9,4]]}},"alternative-id":["10.1126\/science.281.5382.1502"],"URL":"https:\/\/doi.org\/10.1126\/science.281.5382.1502","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,9,4]]}}}