ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL
- Research Institute of Molecular Pathology, Austria
- Baylor College of Medicine, United States
- Stanford University, United States
- University of Birmingham, United Kingdom
- The Francis Crick Institute, United Kingdom
- The Babraham Institute, United Kingdom
- University of Washington, United States
- Gregor Mendel Institute of Molecular Plant Biology, Austria
- Institute of Molecular Biotechnology, Austria
Abstract
Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin's chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.
Data availability
Sequencing data have been deposited in GEO under accession code GSE138405. Please go to https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138405
-
ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPLGene Expression Omnibus (GEO), GSE138405.
Article and author information
Author details
Stefan Schoenfelder
Jan-Michael Peters
Funding
NIH Clinical Center (5U01HL130010-05)
- Erez Lieberman-Aiden
The Austrian Science Fund (Z196-B20 Wittgenstein award)
- Jan-Michael Peters
The European community's Seventh Frame- work Programme (FP7/2007-2013 241548)
- Jan-Michael Peters
Human Frontier Science Program (RGP0057/2018)
- Jan-Michael Peters
NIH Clinical Center (5UM1HG009375-03)
- Erez Lieberman-Aiden
National Science Foundation (PHY-1427654)
- Erez Lieberman-Aiden
Horizon 2020 Framework Programme (EPIC-XS 823839)
- Karl Mechtler
Austrian Science Fund by ERA-CAPS (3686 International Project)
- Karl Mechtler
H2020 European Research Council (No 693949)
- Jan-Michael Peters
Vienna Science and Technology Fund (WWTF LS09-13)
- Jan-Michael Peters
The Austrian Science Fund (SFB F34)
- Jan-Michael Peters
Austrian Research Promotion Agency (FFG-852936)
- Jan-Michael Peters
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeannie T Lee, Massachusetts General Hospital, United States
Publication history
- Received: September 22, 2019
- Accepted: February 10, 2020
- Accepted Manuscript published: February 17, 2020 (version 1)
- Version of Record published: March 3, 2020 (version 2)
- Version of Record updated: March 6, 2020 (version 3)
Copyright
© 2020, Wutz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,661
- Page views
-
- 851
- Downloads
-
- 57
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL
eLife 9:e52091.
https://doi.org/10.7554/eLife.52091
Further reading
-
- Cell Biology
- Immunology and Inflammation
The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.
-
- Cell Biology
- Developmental Biology
Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, its function in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes in Prdx5 knockout (Prdx5Ko) male mice. To investigate the function of Prdx5 in the bone, osteoblasts were analyzed through immunoprecipitation (IP) and liquid chromatography combined with tandem mass spectrometry (LC–MS/MS) methods, while osteoclasts were analyzed through RNA-sequencing. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiation in vitro. Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Bglap) expression. In addition, transcriptomic analysis revealed that in vitro differentiated osteoclasts from the bone marrow-derived macrophages of Prdx5Ko mice showed enhanced expression of several osteoclast-related genes. These findings indicate that Prdx5 might contribute to the maintenance of bone homeostasis by regulating osteoblast differentiation. This study proposes a new function of Prdx5 in bone remodeling that may be used in developing therapeutic strategies for bone diseases.
