Polycomb and Notch signaling regulate cell proliferation potential during<i>Caenorhabditis elegans</i>life cycle

Coraggio, F; Püschel, Ringo; Marti, Alisha; Meister, Peter

doi:10.26508/lsa.201800170

“…LIN-12 Notch signaling is not only critical during the AC/VU decision, but it also links differentiation to cell cycle progression in different tissues [4,26,27]. We therefore tested whether [28].…”

Section: Egl-43 Inhibits Ac Proliferation By Repressing Lin-12 Notch mentioning

confidence: 99%

“…Thus, LIN-12 is an essential downstream target of EGL-43 that can reactivate the cell cycle in the AC. A recent study in C. elegans has highlighted the importance of the LIN-12 Notch pathway in keeping an equilibrium between the proliferation and differentiation of somatic cells [27]. Furthermore, the regulation of different cell cycle genes by the Notch pathway has been reported in several cases.…”

Section: Plos Geneticsmentioning

confidence: 99%

The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

Deng

¹

,

Stempor

²

,

Appert

³

et al. 2020

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Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest.

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“…The ectopic activation of Notch signaling in the differentiated AC was sufficient to induce proliferation in the presence of EGL-43 expression, indicating that LIN-12 acts downstream of EGL-43 to reactivate the cell cycle in the AC. Likewise, a recent study in C. elegans has highlighted the importance of the LIN-12 Notch pathway in keeping an equilibrium between the proliferation and differentiation of somatic cells [23].…”

Section: Discussionmentioning

confidence: 99%

“…LIN-12 Notch signaling is not only critical during the AC/VU decision, but it also links cell differentiation to cell cycle progression in different other tissues [4,22,23]. We therefore tested whether egl-43 regulates lin-12 Notch expression in the AC by examining a translational LIN-12::GFP reporter [24].…”

Section: Egl-43 Inhibits Ac Proliferation By Repressing Lin-12 Notch mentioning

confidence: 99%

The C. elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

Deng

¹

,

Daube

²

,

Hajnal

³

et al. 2019

Preprint

1

0

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Cell invasion allows cells to migrate across compartment boundariesformed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as a critical factor coordinating cell invasion with cell cycle arrest. Author summary Cells invasion is a fundamental biological process that allows cells to cross compartment boundaries and migrate to new locations. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells.We have investigated how a specialized cell in the Nematode C. elegans, the so-called anchor cell, can invade into an adjacent epithelium. Our work has identified an oncogenic transcription factor that controls the expression of specific target genes necessary for cell invasion, and at the same time inhibits the proliferation of the invading anchor cell. These findings shed light on the mechanisms, by which cells decide whether to proliferate or invade.Deng et al.

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“…One fruitful avenue will be to take advantage of the screening capabilities of C. elegans to identify modifiers of chromatin factor-mediated reprogramming. Such efforts have already identified connections between H3K27 methylation, the highly conserved Notch signaling pathway, and control of cell proliferation (Seelk et al, 2016;Coraggio et al, 2019). Another challenge will be to determine the mechanisms underlying cell type-specific reprogramming, and to connect the cell fate phenotypes to broad disruption of chromatin organization, or to misregulation of specific target genes.…”

Section: Functional Consequences Of Regulation By Chromo Domain Protementioning

confidence: 99%

Emerging Roles for Chromo Domain Proteins in Genome Organization and Cell Fate in C. elegans

DasGupta

¹

,

Lee

²

,

Li

³

et al. 2020

Front. Cell Dev. Biol.

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In most eukaryotes, the genome is packaged with histones and other proteins to form chromatin. One of the major mechanisms for chromatin regulation is through post-translational modification of histone proteins. Recognition of these modifications by effector proteins, often dubbed histone "readers," provides a link between the chromatin landscape and gene regulation. The diversity of histone reader proteins for each modification provides an added layer of regulatory complexity. In this review, we will focus on the roles of chromatin organization modifier (chromo) domain containing proteins in the model nematode, Caenorhabditis elegans. An amenability to genetic and cell biological approaches, well-studied development and a short life cycle make C. elegans a powerful system to investigate the diversity of chromo domain protein functions in metazoans. We will highlight recent insights into the roles of chromo domain proteins in the regulation of heterochromatin and the spatial conformation of the genome as well as their functions in cell fate, fertility, small RNA pathways and transgenerational epigenetic inheritance. The spectrum of different chromatin readers may represent a layer of regulation that integrates chromatin landscape, genome organization and gene expression.

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Polycomb and Notch signaling regulate cell proliferation potential duringCaenorhabditis eleganslife cycle

Abstract: Caenorhabditis elegans lineage is invariant between animals. By challenging cell fate in differentiated worms, an unexpected role of Polycomb and Notch signaling in the control of cell proliferation was uncovered, suggesting that the lineage is more flexible than believed.

Cited by 8 publications

References 49 publications

The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

The C. elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

Emerging Roles for Chromo Domain Proteins in Genome Organization and Cell Fate in C. elegans

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