scholarly journals Genomic insights into chromatin reprogramming to totipotency in embryos

2018 ◽  
Vol 218 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Sabrina Ladstätter ◽  
Kikuë Tachibana
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Epigenetic Reprogramming ◽  
Mammalian Embryo ◽  
Cell Fate Decisions ◽  
A Cell ◽  
Early Mouse ◽  
Chromatin Reprogramming

The early embryo is the natural prototype for the acquisition of totipotency, which is the potential of a cell to produce a whole organism. Generation of a totipotent embryo involves chromatin reorganization and epigenetic reprogramming that alter DNA and histone modifications. Understanding embryonic chromatin architecture and how this is related to the epigenome and transcriptome will provide invaluable insights into cell fate decisions. Recently emerging low-input genomic assays allow the exploration of regulatory networks in the sparsely available mammalian embryo. Thus, the field of developmental biology is transitioning from microscopy to genome-wide chromatin descriptions. Ultimately, the prototype becomes a unique model for studying fundamental principles of development, epigenetic reprogramming, and cellular plasticity. In this review, we discuss chromatin reprogramming in the early mouse embryo, focusing on DNA methylation, chromatin accessibility, and higher-order chromatin structure.

scholarly journals The people behind the papers – Megan Rommelfanger and Adam MacLean

Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Cell Communication ◽  
Multiscale Model ◽  
Assistant Professor ◽  
Cell Fate Decisions ◽  
The People ◽  
A Cell ◽  
Internal And External Factors ◽  
External Signals

Cell fate decisions are dependent on both internal and external factors, but mathematical models of this process have often neglected the external signals. A new paper in Development describes a multiscale model that integrates intracellular gene regulatory networks with a cell-cell communication network at single-cell resolution. We caught up with the authors, PhD student Megan Rommelfanger and Adam MacLean, Assistant Professor at the University of Southern California, to find out more about their research.

scholarly journals Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jan J Zylicz ◽  
Sabine Dietmann ◽  
Ufuk Günesdogan ◽  
Jamie A Hackett ◽  
Delphine Cougot ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Histone H3 ◽  
Epigenetic Mechanism ◽  
Mouse Development ◽  
Germline Development ◽  
Chromatin Dynamics ◽  
Cell Fate Decisions ◽  
Active Enhancer ◽  
Early Mouse

Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with redistribution of enhancer of zeste homolog 2 (EZH2)-dependent histone H3 lysine 27 trimethylation (H3K27me3). Loss of G9a or EZH2 results in upregulation of distinct gene sets involved in cell cycle regulation, germline development and embryogenesis. Notably, the H3K9me2 modification extends to active enhancer elements where it promotes developmentally-linked gene silencing and directly marks promoters and gene bodies. This epigenetic mechanism is important for priming gene regulatory networks for critical cell fate decisions in rapidly proliferating postimplantation epiblast cells.

scholarly journals The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch

2021 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Mohammad N. Qasim ◽  
Ashley Valle Arevalo ◽  
Clarissa J. Nobile ◽  
Aaron D. Hernday
Keyword(s):  
Candida Albicans ◽  
Cell Fate ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Chromatin Remodelers ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Simple Model System

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.

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 Single-cell transcriptional analysis to uncover regulatory circuits driving cell fate decisions in early mouse development

2014 ◽  
Vol 31 (7) ◽  
pp. 1060-1066 ◽  
Author(s):  
Haifen Chen ◽  
Jing Guo ◽  
Shital K. Mishra ◽  
Paul Robson ◽  
Mahesan Niranjan ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Transcriptional Analysis ◽  
Mouse Development ◽  
Cell Fate Decisions ◽  
Regulatory Circuits ◽  
Early Mouse

scholarly journals Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development

2000 ◽  
Vol 14 (16) ◽  
pp. 2072-2084
Author(s):  
Babette S. Heyer ◽  
Alasdair MacAuley ◽  
Ole Behrendtsen ◽  
Zena Werb
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Genotoxic Stress ◽  
Embryonic Cells ◽  
Mouse Development ◽  
Potential Cost ◽  
Proliferation And Differentiation ◽  
A Cell ◽  
Early Mouse ◽  
Surveillance Mechanism

Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mouse gastrulation. During this restricted developmental window, the embryo becomes hypersensitive to DNA damage induced by low dose irradiation (<0.5 Gy) and undergoes apoptosis without cell cycle arrest. Intriguingly, embryonic cells, including germ cell progenitors, but not extraembryonic cells, become hypersensitive to genotoxic stress and undergo Atm- and p53-dependent apoptosis. Thus, hypersensitivity to apoptosis in the early mouse embryo is a cell fate-dependent mechanism to ensure genomic integrity during a period of extreme proliferation and differentiation.

Epigenetic Regulation and Risk Factors During the Development of Human Gametes and Early Embryos

2019 ◽  
Vol 20 (1) ◽  
pp. 21-40 ◽  
Author(s):  
Yang Wang ◽  
Qiang Liu ◽  
Fuchou Tang ◽  
Liying Yan ◽  
Jie Qiao
Keyword(s):  
Risk Factors ◽  
Embryo Development ◽  
Current Knowledge ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Epigenetic Reprogramming ◽  
Developmental Defects ◽  
Early Embryo Development ◽  
Potential Risk Factors ◽  
Molecular Layers

Drastic epigenetic reprogramming occurs during human gametogenesis and early embryo development. Advances in low-input and single-cell epigenetic techniques have provided powerful tools to dissect the genome-wide dynamics of different epigenetic molecular layers in these processes. In this review, we focus mainly on the most recent progress in understanding the dynamics of DNA methylation, chromatin accessibility, and histone modifications in human gametogenesis and early embryo development. Deficiencies in remodeling of the epigenomes can cause severe developmental defects, infertility, and long-term health issues in offspring. Aspects of the external environment, including assisted reproductive technology procedures, parental diets, and unhealthy parental habits, may disturb the epigenetic reprogramming processes and lead to an aberrant epigenome in the offspring. Here, we review the current knowledge of the potential risk factors of aberrant epigenomes in humans.

United colours of chromatin? Developmental genome organisation in flies

2019 ◽  
Vol 47 (2) ◽  
pp. 691-700
Author(s):  
Caroline Delandre ◽  
Owen J. Marshall
Keyword(s):  
Cell Fate ◽  
Fruit Fly ◽  
Genome Organisation ◽  
Chromatin Protein ◽  
Cell Type ◽  
Chromatin States ◽  
Cell Fate Decisions ◽  
A Cell ◽  
Cell Type Specific ◽  
Chromatin Biology

Abstract The organisation of DNA into differing forms of packaging, or chromatin, controls many of the cell fate decisions during development. Although early studies focused on individual forms of chromatin, in the last decade more holistic studies have attempted to determine a complete picture of the different forms of chromatin present within a cell. In the fruit fly, Drosophila melanogaster, the study of chromatin states has been aided by the use of complementary and cell-type-specific techniques that profile the marks that recruit chromatin protein binding or the proteins themselves. Although many questions remain unanswered, a clearer picture of how different chromatin states affect development is now emerging, with more unusual chromatin states such as Black chromatin playing key roles. Here, we discuss recent findings regarding chromatin biology in flies.

scholarly journals AtNSE1 and AtNSE3 are required for embryo pattern formation and maintenance of cell viability during Arabidopsis embryogenesis

2019 ◽  
Vol 70 (21) ◽  
pp. 6229-6244
Author(s):  
Gang Li ◽  
Wenxuan Zou ◽  
Liufang Jian ◽  
Jie Qian ◽  
Jie Zhao
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cell Fate ◽  
Embryo Development ◽  
Higher Plants ◽  
Early Embryo ◽  
Embryo Cell ◽  
Early Embryogenesis ◽  
Embryo Abortion ◽  
Cell Fate Decisions

Abstract Embryogenesis is an essential process during seed development in higher plants. It has previously been shown that mutation of the Arabidopsis non-SMC element genes AtNSE1 or AtNSE3 leads to early embryo abortion, and their proteins can interact with each other directly. However, the crucial regions of these proteins in this interaction and how the proteins are cytologically involved in Arabidopsis embryo development are unknown. In this study, we found that the C-terminal including the Ring-like motif of AtNSE1 can interact with the N-terminal of AtNSE3, and only the Ring-like motif is essential for binding with three α motifs of AtNSE2 (homologous to AtMMS21). Using genetic assays and by analysing molecular markers of cell fate decisions (STM, WOX5, and WOX8) in mutant nse1 and nse3 embryos, we found that AtNSE1 and AtNSE3 work non-redundantly in early embryo development, and that differentiation of the apical meristem and the hypophysis fails in the mutants, which have disrupted auxin transportation and responses. However, the upper cells of the suspensor in the mutants seem to have proper embryo cell identity. Cytological examination showed that cell death occurred from the early embryo stage, and that vacuolar programmed cell death and necrosis in the nse1 and nse3 mutant embryos led to ovule abortion. Thus, AtNSE1 and AtNSE3 are essential for maintaining cell viability and growth during early embryogenesis. Our results improve our understanding of the functions of SMC5/6 complex in early embryogenesis in Arabidopsis.

scholarly journals Stochastic antagonism between two proteins governs a bacterial cell fate switch

Science ◽  
2019 ◽  
Vol 366 (6461) ◽  
pp. 116-120 ◽  
Author(s):  
Nathan D. Lord ◽  
Thomas M. Norman ◽  
Ruoshi Yuan ◽  
Somenath Bakshi ◽  
Richard Losick ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Cell Types ◽  
Feedback Loops ◽  
Cell Fate Determination ◽  
Cell Fate Decision ◽  
A Cell ◽  
Fate Decision ◽  
Antagonistic Interactions

Cell fate decision circuits must be variable enough for genetically identical cells to adopt a multitude of fates, yet ensure that these states are distinct, stably maintained, and coordinated with neighboring cells. A long-standing view is that this is achieved by regulatory networks involving self-stabilizing feedback loops that convert small differences into long-lived cell types. We combined regulatory mutants and in vivo reconstitution with theory for stochastic processes to show that the marquee features of a cell fate switch in Bacillus subtilis—discrete states, multigenerational inheritance, and timing of commitments—can instead be explained by simple stochastic competition between two constitutively produced proteins that form an inactive complex. Such antagonistic interactions are commonplace in cells and could provide powerful mechanisms for cell fate determination more broadly.

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