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

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

PROVIDER: PRJNA600737 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10874216_1.fastq.gz	Fastqsanger.gz
	SRR10874216_2.fastq.gz	Fastqsanger.gz
	SRR10874217_1.fastq.gz	Fastqsanger.gz
	SRR10874217_2.fastq.gz	Fastqsanger.gz
	SRR10874218_1.fastq.gz	Fastqsanger.gz

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

Project description:In this study, we have mapped the binding sites for the MTBP subunit of the Treslin-MTBP complex throughout the human genome by using the CUT&RUN method. Our results have indicated that MTBP associates reproducibly with several tens of thousands of sites in the genome. Many binding sites contain either G4 DNA or an AP-1 motif in a nucleosome-free region at transcription start sites (TSSs) or enhancers, respectively. In addition, this nucleosome-free region is adjacent to a nucleosome containing certain histone marks characteristic of open chromatin that have also been implicated in initiation. We also mapped early initiation zones with EdU-labeling (EdU-seq) and found that these initiation domains contain a large number of MTBP binding sites. Taken together, these findings indicate that Treslin-MTBP associates with multiple genomic signals to promote initiation of replication.

2020-09-22 | GSE143481 | GEO

The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition

Project description:It has been proposed that ATR kinase senses the completion of DNA replication to initiate the S/G2 transition. In contrast to this model, we show here that the TRESLIN-MTBP complex prevents a premature entry into G2 from early S-phase independently of ATR/CHK1 kinases. TRESLIN-MTBP acts transiently at pre-replication complexes (preRCs) to initiate origin firing and is released after the subsequent recruitment of CDC45. This dynamic behavior of TRESLIN-MTBP implements a monitoring system that checks the activation of replication forks and senses the rate of origin firing to prevent the entry into G2. This system detects the decline in the number of origins of replication that naturally occurs in very late S, which is the signature that cells use to determine the completion of DNA replication and permit the S/G2 transition. Our work introduces TRESLIN-MTBP as a key player in cell cycle control independent of canonical checkpoints.

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TICRR/TRESLIN and MTBP Cut&Run in Asynchronously Cycling HCT116 Cells

Project description:The selection of replication origins plays a crucial role in eukaryotic DNA replication. However, the mechanisms of origin selection in humans are not yet well-defined. Recent work in yeast has shown that the recruitment of Sld3-Sld7 to origins during G1 is involved in origin selection. In humans, TICRR/TRESLIN and MTBP are the orthologs of Sld3 and Sld7, respectively. In this study, we have mapped the genomic binding locations of TICRR/TRESLIN and MTBP in asynchronous cells.

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Project description:The selection of replication origins plays a crucial role in eukaryotic DNA replication. However, the mechanisms of origin selection in humans still need to be defined. Recent work in yeast has shown that the recruitment of Sld3-Sld7 to origins during G1 is involved in origin selection. In humans, TICRR/TRESLIN and MTBP are the orthologs of Sld3 and Sld7, respectively. In this study, we have mapped the genomic binding locations of TICRR/TRESLIN and MTBP in cells where loading of MCM2-7 complex has been inhibited by dox-inducible expression of a degradation-resistant Geminin(T25D).

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The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition

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TICRR/TRESLIN and MTBP Cut&Run in Asynchronously Cycling HCT116 Cells

Project description:TICRR/TRESLIN and MTBP Cut&Run in Asynchronously Cycling HCT116 Cells

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

Project description: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.

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TICRR/TRESLIN and MTBP Cut&Run in G1 synchronized HCT 116 cells

Project description:TICRR/TRESLIN and MTBP Cut&Run in G1 synchronized HCT 116 cells

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