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Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

ABSTRACT: Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

PROVIDER: PRJNA374343 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5245220_1.fastq.gz	Fastqsanger.gz
	SRR5245220_2.fastq.gz	Fastqsanger.gz
	SRR5245230_1.fastq.gz	Fastqsanger.gz
	SRR5245230_2.fastq.gz	Fastqsanger.gz
	SRR5245240_1.fastq.gz	Fastqsanger.gz

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Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae (HTS)

Project description:Forkhead Box (Fox) proteins share the Forkhead domain, a winged-helix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to developmental defects, cancer, and aging. We recently identified S. cerevisiae Fkh1 and Fkh2 as required for the clustering of a subset of replication origins in G1 phase and for the early initiation of these origins in the ensuing S phase, suggesting a mechanistic role linking the spatial organization of the origins and their activity. Here we show that Fkh1 and Fkh2 share a unique structural feature of human FoxP proteins that enables FoxP2 and FoxP3 to form domain-swapped dimers capable of bridging two DNA molecules in vitro. Accordingly, Fkh1 self-associates in vitro and in vivo in a manner dependent on the conserved domain-swapping region, strongly suggestive of homo-dimer formation. Fkh1- and Fkh2-domain-swap-minus (dsm) mutations are functional as transcription factors yet are defective in replication origin timing control. Fkh1-dsm binds replication origins in vivo but fails to cluster them, supporting the conclusion that Fkh1 and Fkh2 dimers perform a structural role in the spatial organization of chromosomal elements with functional importance.

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Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae (ChIP-chip)

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Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

Project description:This SuperSeries is composed of the SubSeries listed below.

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Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in <i>S. cerevisiae</i>.

Project description:Forkhead Box (Fox) proteins share the Forkhead domain, a winged-helix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to developmental defects, cancer, and aging. We recently identified Saccharomyces cerevisiae Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2) as required for the clustering of a subset of replication origins in G1 phase and for the early initiation of these origins in the ensuing S phase, suggesting a mechanistic role linking the spatial organization of the origins and their activity. Here, we show that Fkh1 and Fkh2 share a unique structural feature of human FoxP proteins that enables FoxP2 and FoxP3 to form domain-swapped dimers capable of bridging two DNA molecules in vitro. Accordingly, Fkh1 self-associates in vitro and in vivo in a manner dependent on the conserved domain-swapping region, strongly suggestive of homodimer formation. Fkh1- and Fkh2-domain-swap-minus (dsm) mutations are functional as transcription factors yet are defective in replication origin timing control. Fkh1-dsm binds replication origins in vivo but fails to cluster them, supporting the conclusion that Fkh1 and Fkh2 dimers perform a structural role in the spatial organization of chromosomal elements with functional importance.

| S-EPMC5373409 | biostudies-literature

Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae [Array Data]

Project description:The replication of eukaryotic chromosomes is organized temporally and spatially within the nucleus through epigenetic regulation of replication origin function. The characteristic initiation timing of specific origins is thought to reflect their chromatin environment or sub-nuclear positioning, however the mechanism remains obscure. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead regulation of origin timing is independent of local levels or changes of transcription. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1-phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. These findings add a new dimension to our understanding of the epigenetic basis for differential origin regulation and its connection to chromosomal domain organization.

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Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae [Sequence Data]

2012-01-20 | GSE33677 | GEO

Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae [Sequence Data]

2012-01-20 | E-GEOD-33677 | biostudies-arrayexpress

Saccharomyces cerevisiae

Project description:Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae (HTS)

| PRJNA374346 | ENA

Saccharomyces cerevisiae

Project description:Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae (ChIP-chip)

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Bacterial artificial chromosomes establish replication timing and sub-nuclear compartment de novo as extra-chromosomal vectors [repli-seq]

Project description:The role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system consisting of ~200kb human bacteria artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) replication origin elements (E-BACs). E-BACs were stably maintained as autonomous mini-chromosomes in both HeLa and human induced pluripotent stem cells (hiPSCs) and established their RT de novo. We applied repli-seq to evaluate E-BACs' replication timing.

2018-01-29 | GSE102522 | GEO

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