Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

Item Type:

Article

Title:

Creators Name:

Barbieri, M. and Xie, S.Q. and Torlai Triglia, E. and Chiariello, A.M. and Bianco, S. and de Santiago, I. and Branco, M.R. and Rueda, D. and Nicodemi, M. and Pombo, A.

Abstract:

Gene expression states influence the 3D conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features that define promoter activation states or binding sites for the transcription factor CTCF. Single-cell imaging of the locus folding was performed to test model predictions. While CTCF occupancy alone fails to predict the in vivo folding at genomic length scale of 10 kb, we found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fiber fully explain the HoxB folding patterns imaged in single cells. We identify state-dependent promoter interactions as major drivers of chromatin folding in gene-dense regions.

Keywords:

Chromatin, Computer Simulation, Confocal Microscopy, DNA, Embryonic Stem Cells, Fluorescence In Situ Hybridization, Fluorescent Antibody Technique, Genetic Loci, Genetic Promoter Regions, Nucleic Acid Conformation, Protein Binding, Single-Cell Analysis, Transcription Factors, Animals, Mice

Source:

Nature Structural & Molecular Biology

ISSN:

1545-9993

Publisher:

Nature Publishing Group

Volume:

Number:

Page Range:

515-524

Date:

June 2017

Official Publication:

https://doi.org/10.1038/nsmb.3402

PubMed:

View item in PubMed

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URL	URL Type
https://edoc.mdc-berlin.de/16391/	Preprint version

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