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Replication dynamics identifies the folding principles of the inactive X chromosome [BrdU-IP Repli-seq]

ABSTRACT: Replication dynamics identifies the folding principles of the inactive X chromosome [BrdU-IP Repli-seq]

PROVIDER: PRJNA870924 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21125000.fastq.gz	Fastqsanger.gz
	SRR21125001.fastq.gz	Fastqsanger.gz
	SRR21125002.fastq.gz	Fastqsanger.gz
	SRR21125003.fastq.gz	Fastqsanger.gz
	SRR21125004.fastq.gz	Fastqsanger.gz

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Replication dynamics identifies the folding principles of the inactive X chromosome [BrdU-IP Repli-seq]

Project description:Chromosome-wide late replication is an enigmatic hallmark of the inactive X chromosome (Xi). How it is established and what it represents remains obscure. By single-cell DNA replication sequencing, here we show that the entire Xi is reorganized to replicate rapidly and uniformly in late S-phase upon X-chromosome inactivation (XCI), reflecting its relatively uniform structure revealed by 4C-seq. Despite this uniformity, only a subset of the Xi became earlier replicating in SmcHD1-mutant cells. In the mutant, these domains protruded out of the Xi core, contacted each other, and became transcriptionally reactivated. 4C-seq suggested that they constituted the outermost layer of the Xi even before XCI and were rich in escape genes. We propose that this default positioning forms the basis for their inherent heterochromatin instability in cells lacking the Xi-binding protein SmcHD1 or exhibiting XCI escape. These observations underscore the importance of 3D genome organization on heterochromatin stability and gene regulation.

2023-07-11 | GSE211570 | GEO

Replication dynamics identifies the folding principles of the inactive X chromosome

Project description:Replication dynamics identifies the folding principles of the inactive X chromosome

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Replication dynamics identifies the folding principles of the inactive X chromosome [4C]

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Replication dynamics identifies the folding principles of the inactive X chromosome [RNA-seq]

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Replication dynamics identifies the folding principles of the inactive X chromosome [scRepli-seq]

Project description:Replication dynamics identifies the folding principles of the inactive X chromosome [scRepli-seq]

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Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization [BrdU-IP Repli-chip]

Project description:Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization [BrdU-IP Repli-chip]

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Replication dynamics identifies the folding principles of the inactive X chromosome

2023-07-11 | GSE211574 | GEO

Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization [BrdU-IP Repli-chip]

Project description:In mammals, chromosomes are partitioned into megabase-sized topologically associating domains (TADs). TADs can be in either A (active) or B (inactive) subnuclear compartments, which correspond to early (E) and late (L) replicating timing (RT) domains, respectively. Here, we show that RT changes are tightly correlated with A/B compartment changes during mouse embryonic stem cell (mESC) differentiation. A/B compartments changed mostly by a “boundary shift,” frequently causing compartment switching of single TADs, which coincided with or preceded RT changes. Upon differentiation, mESCs acquired an A/B compartment organization that closely resembled EpiSCs (epiblast-derived stem cells), suggesting that accumulation of compartment boundary repositioning eventually led to naïve-to-primed pluripotency transition in A/B compartment organization. We propose that large-scale reorganization of A/B compartments, which is reflected in RT domain reorganization, represents major cell fate changes. Collectively, our data provides valuable insights into the regulatory principles of 3-dimensional (3D) genome organization during early embryonic stages.

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Replication dynamics identifies the folding principles of the inactive X chromosome [4C]

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