Precise switching of DNA replication timing in the GC content transition area in the human major histocompatibility complex

Toyoaki Tenzen*, Tetsushi Yamagata, Tatsuo Fukagawa, Kimihiko Sugaya, Asako Ando, Hidetoshi Inoko, Takashi Gojobori, Asao Fujiyama, Katsuzumi Okumura, Toshimichi Ikemura

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

The human genome is composed of long-range G+C% (GC%) mosaic structures thought to be related to chromosome bands. We previously reported a boundary of megabase-sized GC% mosaic domains at the junction area between major histocompability complex (MHC) classes II and III, proposing it as a possible chromosome band boundary. DNA replication timing during the S phase is known to be correlated cytogenetically with chromosome band zones, and thus the band boundaries have been predicted to contain a switch point for DNA replication timing. In this study, to identify to the nucleotide sequence level the replication switch point during the S phase, we determined the precise DNA replication timing for MHC classes II and III, focusing on the junction area. To do this, we used PCR-based quantitation of nascent DNA obtained from synchronized human myeloid leukemia HL60 cells. The replication timing changed precisely in the boundary region with a 2-h difference between the two sides, supporting the prediction that this region may be a chromosome band boundary. We supposed that replication fork movement terminates (pauses) or significantly slows in the switch region, which contains dense Alu clusters; polypurine/polypyrimidine tracts; di-, tri-, or tetranucleotide repeats; and medium-reiteration-frequency sequences. Because the nascent DNA in the switch region was recovered at low efficiency, we investigated whether this region is associated with the nuclear scaffold and found three scaffold- associated regions in and around the switch region.

Original languageEnglish (US)
Pages (from-to)4043-4050
Number of pages8
JournalMolecular and Cellular Biology
Volume17
Issue number7
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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