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LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing [Repli-seq]

ABSTRACT: LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing [Repli-seq]

PROVIDER: PRJNA661444 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12588570_1.fastq.gz	Fastqsanger.gz
	SRR12588570_2.fastq.gz	Fastqsanger.gz
	SRR12588571_1.fastq.gz	Fastqsanger.gz
	SRR12588571_2.fastq.gz	Fastqsanger.gz
	SRR12588572_1.fastq.gz	Fastqsanger.gz

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LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing [Repli-seq]

Project description:The chromatin-based rules governing the selection and activation of replication origins remain to be elucidated. It is believed that DNA replication initiates from open chromatin domains, thus replication origins residing in regulatory elements that are located at open and active chromatin. However, we report here that lysine specific demethylase 1 (LSD1), which biochemically catalyzes H3K4me1/2 demethylation to favor chromatin condensation, interacts with the DNA replication machinery. We found that LSD1 level peaks in early S phase. We demonstrated that LSD1 promotes DNA replication by facilitating origin firing in euchromatic regions and through regulating replication timing. Indeed, euchromatic zones enriched in H3K4me2 are the preferred sites for pre-RC binding in early replication. Remarkably, LSD1 deficiency leads to a genome-wide switch from early to late in replication timing. We showed that LSD1-promoted DNA replication is mechanistically linked to the loading of TICRR (TopBP1-Interacting Checkpoint and Replication Regulator) onto the pre-RC and subsequent recruitment of the initiator Cdc45 during origin firing. Together, these results reveal an unexpected role for LSD1 in euchromatic origin firing and replication timing.

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LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing

Project description:LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing

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LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing [ChIP-seq]

Project description:LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing [ChIP-seq]

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LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing [RNA-seq]

Project description:LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing [RNA-seq]

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LSD1 is required for euchromatic origin firing and replication timing.

Project description:The chromatin-based rule governing the selection and activation of replication origins remains to be elucidated. It is believed that DNA replication initiates from open chromatin domains; thus, replication origins reside in open and active chromatin. However, we report here that lysine-specific demethylase 1 (LSD1), which biochemically catalyzes H3K4me1/2 demethylation favoring chromatin condensation, interacts with the DNA replication machinery in human cells. We find that LSD1 level peaks in early S phase, when it is required for DNA replication by facilitating origin firing in euchromatic regions. Indeed, euchromatic zones enriched in H3K4me2 are the preferred sites for the pre-replicative complex (pre-RC) binding. Remarkably, LSD1 deficiency leads to a genome-wide switch of replication from early to late. We show that LSD1-engaged DNA replication is mechanistically linked to the loading of TopBP1-Interacting Checkpoint and Replication Regulator (TICRR) onto the pre-RC and subsequent recruitment of CDC45 during origin firing. Together, these results reveal an unexpected role for LSD1 in euchromatic origin firing and replication timing, highlighting the importance of epigenetic regulation in the activation of replication origins. As selective inhibitors of LSD1 are being exploited as potential cancer therapeutics, our study supports the importance of leveraging an appropriate level of LSD1 to curb the side effects of anti-LSD1 therapy.

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LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing

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Project description:Mouse ESC 46C replication timing has been assessed by repli-chip.

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