Targeted DamID in
            <i>C. elegans</i>
            reveals a direct role for LIN-22 and NHR-25 in antagonizing the epidermal stem cell fate

Katsanos, Dimitris; Barkoulas, Michalis

doi:10.1126/sciadv.abk3141

Cited by 14 publications

(8 citation statements)

References 61 publications

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“…Currently, ChIP-seq is the most commonly used method to identify binding targets (Kudron et al, 2018;Celniker et al, 2009). Recent studies presented here indicated that TaDa is comparable with ChIP-seq in identifying target genes (Katsanos & Barkoulas, 2022). In addition, TaDa offers the following two key advantages.…”

Section: Discussionmentioning

confidence: 87%

Polycombregulates circadian rhythms inDrosophilain clock neurons

Zhao,

Yang,

et al. 2023

Life Sci. Alliance

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Circadian rhythms are essential physiological feature for most living organisms. Previous studies have shown that epigenetic regulation plays a crucial role. There is a knowledge gap in the chromatin state of some key clock neuron clusters. In this study, we show that circadian rhythm is affected by the epigenetic regulatorPolycomb(Pc) within theDrosophilaclock neurons. To investigate the molecular mechanisms underlying the roles ofPcin these clock neuron clusters, we use targeted DamID (TaDa) to identify genes significantly bound by Pc in the neurons marked byC929-Gal4(including l-LNvs cluster),R6-Gal4(including s-LNvs cluster),R18H11-Gal4(including DN1 cluster), andDVpdf-Gal4,pdf-Gal80(including LNds cluster). It shows that Pc binds to the genes involved in the circadian rhythm pathways, arguing a direct role forPcin regulating circadian rhythms through specific clock genes. This study shows the identification of Pc targets in the clock neuron clusters, providing potential resource for understanding the regulatory mechanisms of circadian rhythms by the PcG complex. Thus, this study provided an example for epigenetic regulation of adult behavior.

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Section: Discussionmentioning

confidence: 87%

Polycombregulates circadian rhythms inDrosophilain clock neurons

Zhao,

Yang,

et al. 2023

Life Sci. Alliance

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“…With the recent report of the wild-type AC transcriptome (Costa et al, 2023) and advancements in single-cell chromatin and transcription factor profiling (Fabian et al, 2022; Katsanos and Barkoulas, 2022; Katsanos et al, 2021; Yee et al, 2023), the application of these genomic profiling technologies should enable a mechanistic understanding of how the invasive differentiation program can be uncoupled from cell cycle exit. We hope that our results will provide a framework for a better understanding of the interplay between cell cycle exit, terminal differentiation, and cell invasion during normal development and disease states such as cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell

Martinez

Zhao

Moore

et al. 2023

Preprint

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The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of C. elegans anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that must exit the cell cycle and enter a post-mitotic to initiate contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the negative cell cycle regulators that maintain the AC in a post-mitotic, invasive state. Although our findings revealed a critical role for CKI-1 (p21CIP1/p27KIP1) in maintaining the post-mitotic state of the AC, loss of CKI-1 alone or in combination with other negative cell cycle regulators-including CKI-2 (p21CIP1/p27KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (Beta-TrCP) resulted in proliferating ACs that retained their invasive abilities. Upon examination of the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs maintain pro-invasive gene expression. We therefore report that maintenance of the post-mitotic state is not necessary for AC invasion, breaking the previously established C. elegans invasion/proliferation dichotomy.

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“…Direct targets of NHR-67 have not yet been discovered, which makes it difficult to investigate this specific aspect of the repressive mechanism at present. We see this as a promising avenue of future study as technologies advance, allowing for transcriptional profiling and target identification in specific tissues or cells (Gómez-Saldivar et al, 2020;Katsanos and Barkoulas, 2022).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation and repressive condensates modulate a proliferative-invasive cellular switch in vivo

Medwig-Kinney

Kinney

Martinez

et al. 2023

Preprint

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A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types that derive from equipotent progenitors, but exhibit distinct cell behaviors, in the developing Caenorhabditis elegans somatic gonad: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We report that the default invasive cellular state is suppressed in the VU cells through two distinct modes of regulation of the pro-invasive transcription factor NHR-67 (NR2E1/TLX). Levels of NHR-67 are important for discriminating between invasive and proliferative behavior, and nhr-67 transcription is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. Residual NHR-67 protein is organized into discrete punctae in the nuclei of VU cells that are dynamic over the cell cycle and exhibit liquid-like properties. Strikingly, these NHR-67 punctae are not spatiotemporally associated with active transcription, but instead associate with homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1, likely mediated by a direct interaction between UNC-37 and the intrinsically disordered region of NHR-67. Further, perturbing UNC-37, LSY-22, or POP-1 results in ectopic invasive cells. We propose a model in which these proteins together form repressive condensates to suppress a default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo.

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Targeted DamID in C. elegans reveals a direct role for LIN-22 and NHR-25 in antagonizing the epidermal stem cell fate

Cited by 14 publications

References 61 publications

Polycombregulates circadian rhythms inDrosophilain clock neurons

Polycombregulates circadian rhythms inDrosophilain clock neurons

Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell

Transcriptional regulation and repressive condensates modulate a proliferative-invasive cellular switch in vivo

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