The coordination of terminal differentiation and cell cycle exit is mediated through the regulation of chromatin accessibility
Posted on: 7 January 2019
Preprint posted on 6 December 2018
Article now published in PLOS Biology at http://dx.doi.org/10.1371/journal.pbio.3000378
Chromatin accessibility on the wing – insights into chromatin regulation of cell cycle exit
Selected by Gabriel AugheyCategories: developmental biology, genetics, molecular biology
Background
The development of complex animal tissues requires the finely tuned expression of thousands of regulatory genes. Changes to underlying chromatin landscape are required to mediate the changes in gene expression necessary for fully differentiated tissues to arise. Consequently, chromatin landscapes are dynamic during development. Whilst it is commonly accepted that accessible or “open” chromatin is associated with regulatory elements that control gene expression, the full relationship between chromatin accessibility and development is incompletely understood.
Much work has been done on understanding the developmental programs that drive differentiation, however the question of how development is brought to a halt at the chromatin level (i.e. terminal differentiation and cell cycle exit) is less well understood. In this preprint, Ma et al. investigate the chromatin changes that accompany wing differentiation in Drosophila and uncover some surprising findings regarding the open chromatin at cell-cycle gene loci.
Key findings
Chromatin accessibility undergoes extensive changes concurrent with altered gene expression during wing development
Ma et al. initially set out to characterise the gene expression and chromatin accessibility profiles of Drosophila wing tissue at various timepoints during development. To achieve this, they conducted RNA-seq and FAIRE-seq at 6 developmental timepoints in the larval and pupal stages (with the final stage comprising post-mitotic differentiated cells). Unsurprisingly, the authors discovered both highly dynamic gene expression and chromatin accessibility landscapes during wing differentiation. Gene expression was correlated to chromatin accessibility and the majority of accessibility changes were observed to be associated with enhancers becoming activated. Importantly, cell-cycle genes were seen to have dynamic regions of open chromatin that correlated with known cell-cycle changes in the developing wing. The critical cell-cycle regulators CycE, stg and e2f1 all exhibited regions in which loss of chromatin accessibility was observed at cell-cycle exit.
Disruption of cell cycle has little impact on chromatin accessibility of cell cycle genes
Having confirmed that chromatin accessibility is correlated with cell-cycle gene expression at cell-cycle exit, the authors sought to understand whether the observed closing of chromatin was a function of cell-cycle exit, or a precursor to it. To answer this question cell cycles were artificially extended through the overexpression of E2F alone or E2F with cyclinD, resulting in either one extra cell division or several rounds of mitoses, respectively. Intriguingly, when wing tissue was profiled by RNA-seq and FAIRE-seq under these conditions, surprisingly few changes to chromatin accessibility were observed, despite extensive changes to gene expression. When several critical cell cycle regulator gene loci were examined in more detail in ectopically cycling tissue (e.g. CycE, stg), chromatin accessibility at putative enhancers was almost indistinguishable from postmitotic cells at the same timepoint (i.e. enhancers continue to be rendered inaccessible despite continued expression of the gene – see figure). This unusual finding suggests that the closing of chromatin is regulated by developmental cues that are not directly linked to the cell-cycle.
Cell cycle disruption impacts accessibility of chromatin at terminal differentiation genes
Whilst changes to chromatin accessibility were not observed at cell cycle genes, the authors went on to show that a subset of genes involved in terminal differentiation displayed a loss of open chromatin when cell cycle exit was delayed compared to controls. These regions largely represented enhancers that were seen to open following cell-cycle exit rather than open regions that became closed as a result of continued cell-cycling. In contrast to the cell cycle genes, this correlated with changes in expression and ultimately resulted in cuticle formation phenotypes.
Why I like this preprint
I found this preprint appealing due to the comprehensive approach the authors have taken to characterise gene expression and chromatin accessibility, resulting in a window into wing development with impressive temporal resolution.
The finding that chromatin accessibility and cell-cycle can be decoupled is surprising and seems to fly in the face of conventional thinking. This new perspective may force us to rethink our ideas about how terminal differentiation is achieved.
Questions for the authors
If chromatin accessibility changes occur independently of cell cycles and are not sufficient to disrupt expression (i.e. CycE is expressed highly in bypassed G0 despite loss of chromatin accessibility – Fig4D), then what is the purpose of the chromatin closing?
Is it possible that the key enhancers for the expression of cell-cycle genes are located distally and act at long range, so are difficult to detect? (i.e. the proximal open chromatin regions observed to be unaffected are redundant with long range enhancers?)
Do you expect that there are changes occurring to histone modifications at cell-cycle loci at which chromatin accessibility appears unaffected by continued cell-cycles?
Do you have any ideas about how the developmental closing of cell cycle genes (i.e. CycE, stg) chromatin is programmed if not directly linked to cell cycle, and do you expect that this will be a conserved mechanism across cell types?
doi: https://doi.org/10.1242/prelights.6812
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the developmental biology category:
Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis
Ankita Walvekar
Actin-based deformations of the nucleus control multiciliated ependymal cell differentiation
Ryan Harrison
HIF1A contributes to the survival of aneuploid and mosaic pre-implantation embryos
Anchel De Jaime Soguero
Also in the genetics category:
Intracellular diffusion in the cytoplasm increases with cell size in fission yeast
Leeba Ann Chacko, Sameer Thukral
Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA
Leeba Ann Chacko
The bat Influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment
Mitchell Sarmie, Mohammed A. Jalloh
Also in the molecular biology category:
Platelet-derived LPA16:0 inhibits adult neurogenesis and stress resilience in anxiety disorder
Harvey Roweth
Green synthesized silver nanoparticles from Moringa: Potential for preventative treatment of SARS-CoV-2 contaminated water
Safieh Shah, Benjamin Dominik Maier
Non-disruptive inducible labeling of ER-membrane contact sites using the Lamin B Receptor
Jonathan Townson
preListsdevelopmental biology category:
in theBSDB/GenSoc Spring Meeting 2024
A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.
List by | Joyce Yu, Katherine Brown |
GfE/ DSDB meeting 2024
This preList highlights the preprints discussed at the 2024 joint German and Dutch developmental biology societies meeting that took place in March 2024 in Osnabrück, Germany.
List by | Joyce Yu |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
2nd Conference of the Visegrád Group Society for Developmental Biology
Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)
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 |
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 |
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 |
Single Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
List by | Alex Eve |
Society for Developmental Biology 79th Annual Meeting
Preprints at SDB 2020
List by | Irepan Salvador-Martinez, Martin Estermann |
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 |
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 |
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. |
EDBC Alicante 2019
Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.
List by | Sergio Menchero 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 |
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
List by | Alex Eve |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
Young Embryologist Network Conference 2019
Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London
List by | Alex Eve |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
List by | Alexa Sadier |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
List by | Dey Lab |
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 genetics category:
BSDB/GenSoc Spring Meeting 2024
A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.
List by | Joyce Yu, Katherine Brown |
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
List by | Reinier Prosee |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
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 |
2nd Conference of the Visegrád Group Society for Developmental Biology
Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)
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. |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
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 |
Also in the molecular biology category:
2024 Hypothalamus GRC
This 2024 Hypothalamus GRC (Gordon Research Conference) preList offers an overview of cutting-edge research focused on the hypothalamus, a critical brain region involved in regulating homeostasis, behavior, and neuroendocrine functions. The studies included cover a range of topics, including neural circuits, molecular mechanisms, and the role of the hypothalamus in health and disease. This collection highlights some of the latest advances in understanding hypothalamic function, with potential implications for treating disorders such as obesity, stress, and metabolic diseases.
List by | Nathalie Krauth |
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
List by | Reinier Prosee |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
List by | Alex Eve, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
List by | Alex Eve |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
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 |