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Post-replicative chromatin accessibility predicts cell fate change.

Teresa E Knudsen1, Nazaret Reverón-Gómez2, Alva Biran2

  • 1The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen, Copenhagen, Denmark; Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.

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Summary
This summary is machine-generated.

DNA replication reconfigures chromatin structure during cell identity changes. This study reveals that replication opens chromatin, creating a window of opportunity for cell fate transitions.

Keywords:
DNA replicationcell fate changechromatin accessibilitydifferentiationrepli-ATAC-seqreprogrammingtranscription factor binding

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Area of Science:

  • Epigenetics and Gene Regulation
  • Developmental Biology
  • Cellular Reprogramming

Background:

  • DNA replication is hypothesized to play a role in chromatin remodeling during cell differentiation and reprogramming.
  • While replication's impact on chromatin structure is known, its functional significance remains unclear.

Purpose of the Study:

  • To investigate the functional role of replication-coupled chromatin changes during cell identity transitions.
  • To determine if DNA replication actively facilitates chromatin accessibility for cell fate determination.

Main Methods:

  • Utilized replication-coupled ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) in differentiating mouse embryonic stem cells and reprogramming fibroblasts.
  • Compared chromatin accessibility in replicated versus unreplicated DNA regions.
  • Assessed the impact of replication inhibition on chromatin opening during reprogramming.

Main Results:

  • Observed de novo chromatin opening exclusively in replicated DNA fractions.
  • The accessibility landscape in replicated regions mimicked later stages of cell differentiation.
  • Lineage-specific transcription factor binding was enriched in replication-opened chromatin regions.
  • Inhibiting DNA replication impaired chromatin opening during early reprogramming.

Conclusions:

  • DNA replication actively drives chromatin opening, establishing an accessible landscape conducive to cell identity changes.
  • Replication creates a critical 'window of opportunity' that promotes chromatin remodeling necessary for development, disease, and reprogramming.
  • This work links replication-induced structural chromatin modifications to functional outcomes in cell fate determination.