title: Regulation of DNA replication timing on human chromosome by a cell-type specific DNA binding protein SATB1.
abstract: BACKGROUND
  Replication timing of metazoan DNA during S-phase may be determined by many factors including chromosome structures, nuclear positioning, patterns of histone modifications, and transcriptional activity. It may be determined by Mb-domain structures, termed as "replication domains", and recent findings indicate that replication timing is under developmental and cell type-specific regulation.
  
  
  RESULTS
  We examined replication timing on the human 5q23/31 3.5-Mb segment in T cells and non-T cells. We used two independent methods to determine replication timing. One is quantification of nascent replicating DNA in cell cycle-fractionated stage-specific S phase populations. The other is FISH analyses of replication foci. Although the locations of early- and late-replicating domains were common between the two cell lines, the timing transition region (TTR) between early and late domains were offset by 200-kb. We show that Special AT-rich sequence Binding protein 1 (SATB1), specifically expressed in T-cells, binds to the early domain immediately adjacent to TTR and delays the replication timing of the TTR. Measurement of the chromosome copy number along the TTR during synchronized S phase suggests that the fork movement may be slowed down by SATB1.
  
  
  CONCLUSIONS
  Our results reveal a novel role of SATB1 in cell type-specific regulation of replication timing along the chromosome.
authors.affiliation: Genome Dynamics Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Oda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanoh
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hisao
authors.initials: H
authors.lastname: Masai
mesh_terms: D020856:AT Rich Sequence / Q000235:genetics; D001665:Binding Sites; D045744:Cell Line, Tumor; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000378:metabolism*; D042522:DNA Replication Timing; D018628:Gene Dosage / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human