Cutting edge Seminar
Speaker: Nozomi Sugimoto (Assistant Professor, Department of Cellular Biochemistry, Faculty of Pharmaceutical Science, Kyushu University)
Title: Genome-wide analysis of the spatiotemporal regulation of firing and dormant replication origins in human cells
Date&Time: 23 Jun. (Wed.) 2021, 12:00- 13:00
※This seminar can also be attended through ZOOM. Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle.
https://md.kumamoto-u.ac.jp/course/view.php?id=90416
Abstract:
DNA replication is a fundamental process required for accurate and timely duplication of chromosomes. During late mitosis to G1 phase, the MCM2-7 complex is loaded onto chromatin in a manner dependent on ORC, CDC6 and Cdt1. In metazoan cells, only a limited number of MCM complexes are fired during S phase, while the majority remain dormant. Several methods have been used to map replication origins, but such methods cannot identify dormant origins. Herein, we determined MCM7-binding sites in human cells using ChIP-seq, classified them into firing and dormant origins using origin data and analysed their association with various chromatin signatures. Firing origins, but not dormant origins, were well correlated with open chromatin regions and were enriched upstream of transcription start sites (TSSs) of transcribed genes. Aggregation plots of MCM7 signals revealed minimal difference in the efficacy of MCM loading between firing and dormant origins. We also analyzed common fragile sites (CFSs) and found a low density of origins at these sites. Nevertheless, firing origins were enriched upstream of the TSSs. Based on the results, we propose a model in which excessive MCMs are actively loaded in a genome-wide manner, irrespective of chromatin status, but only a fraction are passively fired in chromatin areas with an accessible open structure, such as regions upstream of TSSs of transcribed genes. This plasticity in the specification of replication origins may minimize collisions between replication and transcription.
References:
- Sugimoto et al., Nucleic Acids Res., 46, 6683-6696, 2018.
- Sugimoto and Fujita, Adv. Exp. Med. Biol. 1042, 61-78, 2017.
- Sugimoto et al., Nucleic Acids Res., 43, 5898-5911, 2015.
