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Nat Commun. 2018 Oct 10;9(1):4189. doi: 10.1038/s41467-018-06666-4.

Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages.

Author information

1
Nuclear Dynamics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
2
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
3
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, QMUL, London, EC1M 6BQ, UK.
4
College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Doha, Qatar.
5
Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK.
6
Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, E1 2AT, UK.
7
Bordeaux Bioinformatics Center, 33076, Bordeaux, France.
8
INSERM ACTION U1218, Institut Bergonié, 33076, Bordeaux, France.
9
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK. myriam.hemberger@babraham.ac.uk.
10
Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK. myriam.hemberger@babraham.ac.uk.
11
Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, E1 2AT, UK. m.branco@qmul.ac.uk.

Abstract

The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes. We find that key TSC genes that are kept repressed in ESCs exhibit interactions between H3K27me3-marked regions in ESCs that depend on Polycomb repressive complex 1. Interactions that are prominent in TSCs are enriched for enhancer-gene contacts involving key TSC transcription factors, as well as TET1, which helps to maintain the expression of TSC-relevant genes. Our work shows that the first developmental cell fate decision results in distinct chromatin conformation patterns establishing lineage-specific contexts involving both repressive and active interactions.

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