scholarly journals Dynamic methylation of histone H3K18 in differentiating Theileria parasites

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kevin Cheeseman ◽  
Guillaume Jannot ◽  
Nelly Lourenço ◽  
Marie Villares ◽  
Jérémy Berthelet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Control Systems ◽  
Cell Fate ◽  
Life Cycles ◽  
Epigenetic Mark ◽  
Lysine Methylation ◽  
Set Domain ◽  
Histone Tails ◽  
Complex Life Cycles ◽  
Intracellular Parasites

AbstractLysine methylation on histone tails impacts genome regulation and cell fate determination in many developmental processes. Apicomplexa intracellular parasites cause major diseases and they have developed complex life cycles with fine-tuned differentiation events. Yet, apicomplexa genomes have few transcription factors and little is known about their epigenetic control systems. Tick-borne Theileria apicomplexa species have relatively small, compact genomes and a remarkable ability to transform leucocytes in their bovine hosts. Here we report enriched H3 lysine 18 monomethylation (H3K18me1) on the gene bodies of repressed genes in Theileria macroschizonts. Differentiation to merozoites (merogony) leads to decreased H3K18me1 in parasite nuclei. Pharmacological manipulation of H3K18 acetylation or methylation impacted parasite differentiation and expression of stage-specific genes. Finally, we identify a parasite SET-domain methyltransferase (TaSETup1) that can methylate H3K18 and represses gene expression. Thus, H3K18me1 emerges as an important epigenetic mark which controls gene expression and stage differentiation in Theileria parasites.

scholarly journals Dynamic methylation of histone H3K18 in differentiating Theileria parasites

2020 ◽  
Author(s):  
Kevin Cheeseman ◽  
Guillaume Jannot ◽  
Nelly Lourenco ◽  
Marie Villares ◽  
Jeremy BERTHELET ◽  
...  
Keyword(s):  
Gene Expression ◽  
Control Systems ◽  
Cell Fate ◽  
Life Cycles ◽  
Epigenetic Mark ◽  
Lysine Methylation ◽  
Set Domain ◽  
Histone Tails ◽  
Complex Life Cycles ◽  
Intracellular Parasites

Abstract Lysine methylation on histone tails impacts genome regulation and cell fate determination in many developmental processes. Apicomplexa intracellular parasites cause major diseases and they have developed complex life cycles with fine-tuned differentiation events. Yet, apicomplexa genomes have few transcription factors and little is known about their epigenetic control systems. Tick-borne Theileria apicomplexa species have relatively small compact genomes and a remarkable ability to transform leukocytes in their bovine hosts. Here we report enriched H3 lysine 18 monomethylation (H3K18me1) on the gene bodies of repressed genes in Theileria macroschizonts. Differentiation to merozoites (merogony) led to decreased H3K18me1 in parasite nuclei. Pharmacological manipulation of H3K18 acetylation or methylation impacted parasite differentiation and expression of stage-specific genes. Finally, we identified a parasite SET-domain methyltransferase (TaSETup1) that can methylate H3K18 and represses gene expression. Thus, H3K18me1 emerges as an important epigenetic mark which controls gene expression and stage differentiation in Theileria parasites.

scholarly journals CENP-A overexpression promotes distinct fates in human cells, depending on p53 status

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Daniel Jeffery ◽  
Alberto Gatto ◽  
Katrina Podsypanina ◽  
Charlène Renaud-Pageot ◽  
Rebeca Ponce Landete ◽  
...  
Keyword(s):  
Cell Fate ◽  
Epithelial Mesenchymal Transition ◽  
Clonogenic Survival ◽  
Response To Therapy ◽  
Epigenetic Mark ◽  
Mammalian Development ◽  
Mesenchymal Transition ◽  
Histone H3 Variant ◽  
Tumour Cell Invasion ◽  
P53 Status

AbstractTumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear. Here, we established a tunable system of inducible and reversible CENP-A overexpression combined with a switch in p53 status in human cell lines. Through clonogenic survival assays, single-cell RNA-sequencing and cell trajectory analysis, we uncover the tumour suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. If p53 is functional, CENP-A overexpression promotes senescence and radiosensitivity. Surprisingly, when we inactivate p53, CENP-A overexpression instead promotes epithelial-mesenchymal transition, an essential process in mammalian development but also a precursor for tumour cell invasion and metastasis. Thus, we uncover an unanticipated function of CENP-A overexpression to promote cell fate reprogramming, with important implications for development and tumour evolution.

scholarly journals Three‐dimensional multi‐gene expression maps reveal cell fate changes associated with laterality reversal of zebrafish habenula

2021 ◽  
Author(s):  
Guo‐Tzau Wang ◽  
He‐Yen Pan ◽  
Wei‐Han Lang ◽  
Yuan‐Ding Yu ◽  
Chang‐Huain Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Three Dimensional

scholarly journals Massively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathan J. VanDusen ◽  
Julianna Y. Lee ◽  
Weiliang Gu ◽  
Catalina E. Butler ◽  
Isha Sethi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Screen ◽  
Forward Genetics ◽  
Epigenetic Mark ◽  
Biological Processes ◽  
Dynamic Changes ◽  
Forward Genetic Screen ◽  
High Resource ◽  
Organ Systems

AbstractThe forward genetic screen is a powerful, unbiased method to gain insights into biological processes, yet this approach has infrequently been used in vivo in mammals because of high resource demands. Here, we use in vivo somatic Cas9 mutagenesis to perform an in vivo forward genetic screen in mice to identify regulators of cardiomyocyte (CM) maturation, the coordinated changes in phenotype and gene expression that occur in neonatal CMs. We discover and validate a number of transcriptional regulators of this process. Among these are RNF20 and RNF40, which form a complex that monoubiquitinates H2B on lysine 120. Mechanistic studies indicate that this epigenetic mark controls dynamic changes in gene expression required for CM maturation. These insights into CM maturation will inform efforts in cardiac regenerative medicine. More broadly, our approach will enable unbiased forward genetics across mammalian organ systems.

scholarly journals GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mika J. Välimäki ◽  
Robert S. Leigh ◽  
Sini M. Kinnunen ◽  
Alexander R. March ◽  
Ana Hernández de Sande ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Reporter Gene ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Decisions ◽  
Dual Reporter ◽  
Gene Regulatory ◽  
Reporter Gene Assays

AbstractBackgroundPharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.MethodsTranscription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.ResultsGATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.ConclusionsCollectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.

scholarly journals Impacts of climate change on the complex life cycles of fish

2012 ◽  
Vol 22 (2) ◽  
pp. 121-139 ◽  
Author(s):  
Pierre Petitgas ◽  
Adriaan D. Rijnsdorp ◽  
Mark Dickey-Collas ◽  
Georg H. Engelhard ◽  
Myron A. Peck ◽  
...  
Keyword(s):  
Climate Change ◽  
Life Cycles ◽  
Complex Life Cycles ◽  
Impacts Of Climate Change

scholarly journals Using single-cell transcriptomics to understand functional states and interactions in microbial eukaryotes

2019 ◽  
Vol 374 (1786) ◽  
pp. 20190098 ◽  
Author(s):  
Chuan Ku ◽  
Arnau Sebé-Pedrós
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Interspecific Interactions ◽  
Single Cells ◽  
Life Cycles ◽  
Modern Biology ◽  
Microbial Eukaryotes ◽  
Eukaryotic Microorganisms

Understanding the diversity and evolution of eukaryotic microorganisms remains one of the major challenges of modern biology. In recent years, we have advanced in the discovery and phylogenetic placement of new eukaryotic species and lineages, which in turn completely transformed our view on the eukaryotic tree of life. But we remain ignorant of the life cycles, physiology and cellular states of most of these microbial eukaryotes, as well as of their interactions with other organisms. Here, we discuss how high-throughput genome-wide gene expression analysis of eukaryotic single cells can shed light on protist biology. First, we review different single-cell transcriptomics methodologies with particular focus on microbial eukaryote applications. Then, we discuss single-cell gene expression analysis of protists in culture and what can be learnt from these approaches. Finally, we envision the application of single-cell transcriptomics to protist communities to interrogate not only community components, but also the gene expression signatures of distinct cellular and physiological states, as well as the transcriptional dynamics of interspecific interactions. Overall, we argue that single-cell transcriptomics can significantly contribute to our understanding of the biology of microbial eukaryotes. This article is part of a discussion meeting issue ‘Single cell ecology’.

Sign in / Sign up

Export Citation Format

Share Document