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LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157471 | GEO | 2022/03/07

REPOSITORIES: GEO

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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.

2022-03-07 | GSE157470 | GEO

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

2022-03-07 | GSE157469 | GEO

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

2022-03-07 | GSE157468 | GEO

LSD1 Facilitates Euchromatic Origin Firing and Regulates Replication Timing

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

| PRJNA661437 | ENA

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

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

| PRJNA661442 | ENA

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

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

| PRJNA661443 | ENA

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

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

| PRJNA661444 | ENA

Linker histone phosphorylation regulates global timing of replication origin firing.

Project description:Despite the presence of linker histone in all eukaryotes, the primary function(s) of this histone have been difficult to clarify. Knock-out experiments indicate that H1s play a role in regulation of only a small subset of genes but are an essential component in mouse development. Here, we show that linker histone (H1) is involved in the global regulation of DNA replication in Physarum polycephalum. We find that genomic DNA of H1 knock-down cells is more rapidly replicated, an effect due at least in part to disruption of the native timing of replication fork firing. Immunoprecipitation experiments demonstrate that H1 is transiently lost from replicating chromatin via a process facilitated by phosphorylation. Our results suggest that linker histones generate a chromatin environment refractory to replication and that their transient removal via protein phosphorylation during S phase is a critical step in the epigenetic regulation of replication timing.

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Rif1 is a global regulator of timing of replication origin firing in fission yeast.

Project description:One of the long-standing questions in eukaryotic DNA replication is the mechanisms that determine where and when a particular segment of the genome is replicated. Cdc7/Hsk1 is a conserved kinase required for initiation of DNA replication and may affect the site selection and timing of origin firing. We identified rif1Δ, a null mutant of rif1(+), a conserved telomere-binding factor, as an efficient bypass mutant of fission yeast hsk1. Extensive deregulation of dormant origins over a wide range of the chromosomes occurs in rif1Δ in the presence or absence of hydroxyurea (HU). At the same time, many early-firing, efficient origins are suppressed or delayed in firing timing in rif1Δ. Rif1 binds not only to telomeres, but also to many specific locations on the arm segments that only partially overlap with the prereplicative complex assembly sites, although Rif1 tends to bind in the vicinity of the late/dormant origins activated in rif1Δ. The binding to the arm segments occurs through M to G1 phase in a manner independent of Taz1 and appears to be essential for the replication timing program during the normal cell cycle. Our data demonstrate that Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes.

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Rif1 regulates initiation timing of late replication origins throughout the S. cerevisiae genome

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-06-01 | E-GEOD-55156 | biostudies-arrayexpress