PMID- 25493640 OWN - NLM STAT- MEDLINE DCOM- 20150916 LR - 20181113 IS - 1949-1042 (Electronic) IS - 1949-1034 (Print) IS - 1949-1034 (Linking) VI - 5 IP - 6 DP - 2014 TI - Functional redundancy in the nuclear compartmentalization of the late-replicating genome. PG - 626-35 LID - 10.4161/19491034.2014.990863 [doi] AB - The eukaryotic nucleus is structurally and functionally organized, as reflected in the distribution of its protein and DNA components. The genome itself is segregated into euchromatin and heterochromatin that replicate in a distinct spatio-temporal manner. We used a combination of fluorescence in situ hybridization (FISH) and DamID to investigate the localization of the early and late replicating components of the genome in a lymphoblastoid cell background. Our analyses revealed that the bulk of late replicating chromatin localizes to the nuclear peripheral heterochromatin (PH) in a chromosome size and gene density dependent manner. Late replicating DNA on small chromosomes exhibits a much lower tendency to localize to PH and tends to associate with alternate repressive subcompartments such as pericentromeric (PCH) and perinucleolar heterochromatin (PNH). Furthermore, multicolor FISH analysis revealed that late replicating loci, particularly on the smaller chromosomes, may associate with any of these 3 repressive subcompartments, including more than one at the same time. These results suggest a functional equivalence or redundancy among the 3 subcompartments. Consistent with this notion, disruption of nucleoli resulted in an increased association of late replicating loci with peripheral heterochromatin. Our analysis reveals that rather than considering the morphologically distinct PH, PCH and PNH as individual subcompartments, they should be considered in aggregate as a functional compartment for late replicating chromatin. FAU - Ragoczy, Tobias AU - Ragoczy T AD - a Division of Basic Sciences ; Fred Hutchinson Cancer Research Center ; Seattle , WA USA. FAU - Telling, Agnes AU - Telling A FAU - Scalzo, David AU - Scalzo D FAU - Kooperberg, Charles AU - Kooperberg C FAU - Groudine, Mark AU - Groudine M LA - eng GR - R01 HL065440/HL/NHLBI NIH HHS/United States GR - R37 DK044746/DK/NIDDK NIH HHS/United States GR - DK44746/DK/NIDDK NIH HHS/United States GR - HL065440/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Nucleus JT - Nucleus (Austin, Tex.) JID - 101518322 RN - 0 (Euchromatin) RN - 0 (Heterochromatin) SB - IM MH - Cell Compartmentation/*genetics MH - Cell Line MH - Cell Nucleus/*genetics/ultrastructure MH - Chromosomes/genetics MH - DNA Replication/*genetics MH - Euchromatin/genetics MH - Genome, Human MH - Heterochromatin/*genetics/ultrastructure MH - Humans MH - In Situ Hybridization, Fluorescence PMC - PMC4615584 OTO - NOTNLM OT - Chr, chromosome OT - DamID OT - DamID, Dam identification OT - EU, 5-Ethynyl uridine OT - FISH, fluorescence in situ hybridization OT - LAD, lamina associated domain OT - NOR, nucleolar organizing region OT - PCH, pericentromeric heterochromatin OT - PH, peripheral heterochromatin OT - PNH, perinucleolar heterochromatin OT - heterochromatin OT - localization OT - nuclear organization OT - nuclear periphery, pericentromeric heterochromatin OT - perinucleolar heterochromatin OT - replication timing OT - repressive compartments EDAT- 2014/12/11 06:00 MHDA- 2015/09/17 06:00 PMCR- 2015/12/10 CRDT- 2014/12/11 06:00 PHST- 2014/12/11 06:00 [entrez] PHST- 2014/12/11 06:00 [pubmed] PHST- 2015/09/17 06:00 [medline] PHST- 2015/12/10 00:00 [pmc-release] AID - 990863 [pii] AID - 10.4161/19491034.2014.990863 [doi] PST - ppublish SO - Nucleus. 2014;5(6):626-35. doi: 10.4161/19491034.2014.990863.