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Binding of the Treslin-MTBP Complex to Specific Regions of the Human Genome Promotes the Initiation of DNA Replication

Kumagai, Akiko and Dunphy, William G. (2020) Binding of the Treslin-MTBP Complex to Specific Regions of the Human Genome Promotes the Initiation of DNA Replication. Cell Reports, 32 (12). Art. No. 108178. ISSN 2211-1247. PMCID PMC7523632. https://resolver.caltech.edu/CaltechAUTHORS:20200924-091021855

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Abstract

The processes that control where higher eukaryotic cells initiate DNA replication throughout the genome are not understood clearly. In metazoans, the Treslin-MTBP complex mediates critical final steps in formation of the activated replicative helicase prior to initiation of replication. Here, we map the genome-wide distribution of the MTBP subunit of this complex in human cells. Our results indicate that MTBP binds to at least 30,000 sites in the genome. A majority of these sites reside in regions of open chromatin that contain transcriptional-regulatory elements (e.g., promoters, enhancers, and super-enhancers), which are known to be preferred areas for initiation of replication. Furthermore, many binding sites encompass two genomic features: a nucleosome-free DNA sequence (e.g., G-quadruplex DNA or AP-1 motif) and a nucleosome bearing histone marks characteristic of open chromatin, such as H3K4me2. Taken together, these findings indicate that Treslin-MTBP associates coordinately with multiple genomic signals to promote initiation of replication.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.celrep.2020.108178DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523632PubMed CentralArticle
ORCID:
AuthorORCID
Kumagai, Akiko0000-0003-2422-8053
Dunphy, William G.0000-0001-7598-8939
Additional Information:© 2020 The Author(s). Under a Creative Commons license - Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Received 17 March 2020, Revised 12 June 2020, Accepted 31 August 2020, Available online 22 September 2020. We are grateful to Xun Wang, Hiroyuki Hosokawa, and Ellen Rothenberg as well as Fan Gao and Lior Pachter (Bioinformatics Resource Center in the Beckman Institute at Caltech) for valuable discussions. Alexander Varshavsky and Ke Lyu provided helpful comments on the manuscript. We also thank Diane Trout for advice about computation and Igor Antoshechkin for DNA sequencing. Imaging studies were performed in the Caltech Biological Imaging Center (supported by the Beckman Institute and the Arnold and Mabel Beckman Foundation). Kanomi Sasaki-Capela provided technical assistance. This work was supported by NIH grants GM043974 and GM070891 to W.G.D. Author Contributions. A.K. and W.G.D. conceived the study; A.K. carried out the experiments; and A.K. and W.G.D. analyzed the data and wrote the paper. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
NIHGM043974
NIHGM070891
Subject Keywords:DNA replication; Treslin; MTBP; CUT&RUN; replication origin
Issue or Number:12
PubMed Central ID:PMC7523632
Record Number:CaltechAUTHORS:20200924-091021855
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200924-091021855
Official Citation:Akiko Kumagai, William G. Dunphy, Binding of the Treslin-MTBP Complex to Specific Regions of the Human Genome Promotes the Initiation of DNA Replication, Cell Reports, Volume 32, Issue 12, 2020, 108178, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2020.108178.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105514
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:24 Sep 2020 20:16
Last Modified:30 Sep 2020 16:09

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