Capturing the onset of PRC2-mediated repressive domain formation
Preprint posted on 27 February 2018 https://www.biorxiv.org/content/early/2018/02/27/272989
Article now published in Molecular Cell at http://dx.doi.org/10.1016/j.molcel.2018.05.023
How does Polycomb initiate and maintain gene silencing? A new preprint identifies a two-step mechanism of H3K27me2/3 domain formation – initial recruitment to spatially interacting sites followed by spreading in cis and via long-range contacts.
Selected by Boyan Bonev
Categories: biochemistry, cell biology, genomics, molecular biology
Why is it important?
Lineage specification depends on the stable and faithful inheritance of gene expression profiles. Epigenetic regulation, including modification of DNA and histones, plays an important role in establishing and maintaining cell fate identity during development. Among those, Polycomb-mediated repressive chromatin state associated with H3K27me2/3 has been extensively studied and many important players have been identified. However, how Polycomb is initially recruited to specific genomic loci in mammals and how this is translated into repressive domains of H3K27me3 remains unclear.
What are the key findings?
In this preprint Reinberg and colleagues develop and employ an inducible system to study the dynamics and the determinants of the initial Polycomb Repressive Complex 2 (PRC2) recruitment and spreading in mouse embryonic stem cells. They discover that PRC2 is first deposited only at a small subset of its binding sites, which are enriched in dense CpG islands. The authors identify the proteins Jarid2 and specifically Mtf2 as essential for this initial PRC2 recruitment. Subsequently, H3K27me3 spreads from these “nucleation sites” both in cis- and via long-range 3D chromatin contacts. Importantly, a mutation in one subunit of the PRC2 complex – Eed, affects the spreading but not the initial binding of PRC2 to the nucleation sites, further suggesting that they represent two temporarily distinct events. Furthermore, using chromatin conformation capture assays they show that spreading of H3K27me3 is facilitated via long-range chromatin interactions and that contacts between “nucleation sites” are partially dependent on polycomb. Finally, using an elegant tethering system they demonstrate that PRC2 activity exploits 3D genome architecture to spread across distal, contacting regions.
Questions arising
Does the spatial clustering of polycomb-associated sites result in liquid phase-separation phenomenon?
What is the molecular mechanism for long-range loop formation between polycomb loci?
Does PRC1 complex also follow similar kinetics for its recruitment and spreading?
Related Research
Schuettengruber, B. et al. Genome Regulation by Polycomb and Trithorax: 70 Years and Counting. Cell 171, 34-57 (2017).
Schoenfelder, S., et. al. & Elderkin, S. Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome . Nat Genetics 47, 1179-1186 (2015).
Posted on: 31 March 2018
Read preprint
(No Ratings Yet)Sign up to customise the site to your preferences and to receive alerts
Register hereAlso in the biochemistry category:
Also in the cell biology category:
Proteolysis-free cell migration through crowded environments via mechanical worrying
| Selected by | Jade Chan |
1
An epigenetic barrier sets the timing of human neuronal maturation
| Selected by | PiCLS Dundee |
1
mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis
| Selected by | Diego Sainz de la Maza |
1
Also in the genomics category:
Dissecting aneuploidy phenotypes by constructing Sc2.0 chromosome VII and SCRaMbLEing synthetic disomic yeast
| Selected by | Grace Heredge Thomas |
Disrupting cellular memory to overcome drug resistance
| Selected by | Nate Mullin |
1
Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals
| Selected by | Carly Guiltinan |
1
Also in the molecular biology category:
ARHGEF18 participates in Endothelial Cell Mechano-sensitivity in Response to Flow
| Selected by | Aarren Mannion |
Targeting a broad spectrum of KRAS-mutant cancers by hyperactivation-induced cell death
| Selected by | Yvonne Xinyi Lim |
1
Disrupting cellular memory to overcome drug resistance
| Selected by | Nate Mullin |
1
preLists in the biochemistry category:
20th “Genetics Workshops in Hungary”, Szeged (25th, September)
In this annual conference, Hungarian geneticists, biochemists and biotechnologists presented their works. Link: http://group.szbk.u-szeged.hu/minikonf/archive/prg2021.pdf
| List by | Nándor Lipták |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
Also in the cell biology category:
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
| List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
| List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
| List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
| List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
| List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
| List by | Dey Lab |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
| List by | Joseph Jose Thottacherry |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
| List by | Dey Lab, Amanda Haage |
Also in the genomics category:
Semmelweis Symposium 2022: 40th anniversary of international medical education at Semmelweis University
This preList contains preprints discussed during the 'Semmelweis Symposium 2022' (7-9 November), organised around the 40th anniversary of international medical education at Semmelweis University covering a wide range of topics.
| List by | Nándor Lipták |
20th “Genetics Workshops in Hungary”, Szeged (25th, September)
In this annual conference, Hungarian geneticists, biochemists and biotechnologists presented their works. Link: http://group.szbk.u-szeged.hu/minikonf/archive/prg2021.pdf
| List by | Nándor Lipták |
EMBL Conference: From functional genomics to systems biology
Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020
| List by | Jesus Victorino |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
Zebrafish immunology
A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.
| List by | Shikha Nayar |
Also in the molecular biology category:
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |