Linking the dynamics of chromatin occupancy and transcription with predictive models

Tran, Trung Q.; MacAlpine, Heather K.; Tripuraneni, Vinay; Mitra, Sneha; MacAlpine, David M.; Hartemink, Alexander J.

doi:10.1101/2020.06.28.176545

Cited by 2 publications

(2 citation statements)

References 91 publications

(175 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increased entropy observed at replication origins in the absence of polymerase α function is analogous to the chromatin changes observed at highly transcribed genes upon induction, such as RNR1. The elevated entropy within gene bodies is driven by the continual unwinding by the RNA polymerase that disrupts nucleosome structure (Tran et al 2020). In contrast, the increased chromatin disorganization and entropy at replication origins is likely driven by CMG-dependent DNA unwinding.…”

Section: Discussionmentioning

confidence: 99%

“…In this model, late origins will not experience chromatin changes, either solely due to the absence of limiting pre-IC factors or due to the additional suppression of late origins by the intra-S-phase checkpoint. To agnostically identify disorganized origins, we developed an entropy score based on information theory to holistically capture chromatin organization (Tran et al 2020). In organized chromatin, fragment midpoints resulting from our MNase assay tend to be well-organized at small factor (e.g.…”

Section: Origin Chromatin Is Disrupted In the Absence Of Cdc17 Functionmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of origin chromatin structure by helicase activation in the absence of DNA replication

Hoffman

MacAlpine

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Prior to initiation of DNA replication, the eukaryotic helicase, Mcm2-7, must be activated to unwind DNA at replication start sites in early S-phase. To study helicase activation within origin chromatin, we constructed a conditional mutant of the polymerase α subunit Cdc17 (or Pol1) to prevent priming and block replication. Recovery of these cells at permissive conditions resulted in the generation of unreplicated gaps at origins, likely due to helicase activation prior to replication initiation. We used micrococcal nuclease (MNase)-based chromatin occupancy profiling under restrictive conditions to study chromatin dynamics associated with helicase activation. Helicase activation in the absence of DNA replication resulted in the disruption and disorganization of chromatin which extends up to one kilobase from early, efficient replication origins. The CMG holo-helicase complex also moves the same distance out from the origin, producing single-stranded DNA that activates the intra-S-phase checkpoint. Loss of the checkpoint did not regulate the progression and stalling of the CMG complex, but rather resulted in the disruption of chromatin at both early and late origins. Finally, we found that the local sequence context regulates helicase progression in the absence of DNA replication, suggesting that the helicase is intrinsically less processive when uncoupled from replication.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Origin Chromatin Is Disrupted In the Absence Of Cdc17 Functionmentioning

confidence: 99%

Disruption of origin chromatin structure by helicase activation in the absence of DNA replication

Hoffman

MacAlpine

2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication

et al. 2021

Self Cite

View full text Add to dashboard Cite

Although the molecular events required for the repair of double-strand breaks (DSB) have been well characterized, the role of epigenetic processes in the recognition and repair of DSBs has only been investigated at low resolution. We rapidly and synchronously induced a site-specific DSB in Saccharomyces cerevisiae upstream of the PHO5 locus, which has well-positioned nucleosomes. Utilizing MNase-seq epigenome mapping we interrogated the order of chromatin changes that occur immediately following a DSB by generating a base-pair resolution map of the chromatin landscape.In wild type cells, the first nucleosome left of the break was rapidly evicted. The eviction of this flanking nucleosome was dynamic and proceeded through an early intermediate chromatin structure where the nucleosome was repositioned in the adjacent linker DNA.Other nucleosomes bordering both sides of the break were also shifted away from the break; however, their loss was more gradual. These local changes preceded a broader loss of chromatin organization and nucleosome eviction that was marked by increased MNase sensitivity in the regions ~8 kb on each side of the break. While the broad loss of chromatin organization was dependent on the end-processing complex, Mre11-Rad50-Xrs2 (MRX), the early remodeling and repositioning of the nucleosome adjacent to the break was independent of the MRX and YKU70/80 complexes. We also examined the temporal dynamics of NHEJ-mediated repair in a G1-arrested population, where 5' to 3' end-resection of DSB ends is blocked. Concomitant with DSB repair, we

show abstract

Linking the dynamics of chromatin occupancy and transcription with predictive models

Cited by 2 publications

References 91 publications

Disruption of origin chromatin structure by helicase activation in the absence of DNA replication

Disruption of origin chromatin structure by helicase activation in the absence of DNA replication

Local nucleosome dynamics and eviction following a double-strand break are reversible by NHEJ-mediated repair in the absence of DNA replication

Contact Info

Product

Resources

About