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Cold Spring Harbor Perspectives in... Feb 2022Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself... (Review)
Review
Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself to form a nuclear subcompartment, the nuclear lamina, that is involved in a variety of cellular processes such as the governance of nuclear integrity, nuclear positioning, mitosis, DNA repair, DNA replication, splicing, signaling, mechanotransduction and -sensation, transcriptional regulation, and genome organization. Lamins are the primary scaffold for this nuclear subcompartment, but interactions with lamin-associated peptides in the inner nuclear membrane are self-reinforcing and mutually required. Lamins also interact, directly and indirectly, with peripheral heterochromatin domains called lamina-associated domains (LADs) and help to regulate dynamic 3D genome organization and expression of developmentally regulated genes.
Topics: Cell Nucleus; Chromatin; Lamins; Mechanotransduction, Cellular; Nuclear Envelope; Nuclear Lamina
PubMed: 34400553
DOI: 10.1101/cshperspect.a040113 -
Reproduction (Cambridge, England) Feb 2021Idiopathic or 'unexplained' infertility represents as many as 30% of infertility cases worldwide. Conception, implantation, and term delivery of developmentally healthy... (Review)
Review
Idiopathic or 'unexplained' infertility represents as many as 30% of infertility cases worldwide. Conception, implantation, and term delivery of developmentally healthy infants require chromosomally normal (euploid) eggs and sperm. The crux of euploid egg production is error-free meiosis. Pathologic genetic variants dysregulate meiotic processes that occur during prophase I, meiotic resumption, chromosome segregation, and in cell cycle regulation. This dysregulation can result in chromosomally abnormal (aneuploid) eggs. In turn, egg aneuploidy leads to a broad range of clinical infertility phenotypes, including primary ovarian insufficiency and early menopause, egg fertilization failure and embryonic developmental arrest, or recurrent pregnancy loss. Therefore, maternal genetic variants are emerging as infertility biomarkers, which could allow informed reproductive decision-making. Here, we select and deeply examine human genetic variants that likely cause dysregulation of critical meiotic processes in 14 female infertility-associated genes: SYCP3, SYCE1, TRIP13, PSMC3IP, DMC1, MCM8, MCM9, STAG3, PATL2, TUBB8, CEP120, AURKB, AURKC, andWEE2. We discuss the function of each gene in meiosis, explore genotype-phenotype relationships, and delineate the frequencies of infertility-associated variants.
Topics: ATPases Associated with Diverse Cellular Activities; Aneuploidy; Aurora Kinase C; Cell Cycle Proteins; Chromosome Segregation; Female; Humans; Infertility, Female; Male; Meiosis; Nuclear Proteins; Pregnancy; Spermatozoa; Trans-Activators; Tubulin
PubMed: 33170803
DOI: 10.1530/REP-20-0422 -
Cell Oct 2021Retrotransposons mediate gene regulation in important developmental and pathological processes. Here, we characterized the transient retrotransposon induction during...
Retrotransposons mediate gene regulation in important developmental and pathological processes. Here, we characterized the transient retrotransposon induction during preimplantation development of eight mammals. Induced retrotransposons exhibit similar preimplantation profiles across species, conferring gene regulatory activities, particularly through long terminal repeat (LTR) retrotransposon promoters. A mouse-specific MT2B2 retrotransposon promoter generates an N-terminally truncated Cdk2ap1 that peaks in preimplantation embryos and promotes proliferation. In contrast, the canonical Cdk2ap1 peaks in mid-gestation and represses cell proliferation. This MT2B2 promoter, whose deletion abolishes Cdk2ap1 production, reduces cell proliferation and impairs embryo implantation, is developmentally essential. Intriguingly, Cdk2ap1 is evolutionarily conserved in sequence and function yet is driven by different promoters across mammals. The distinct preimplantation Cdk2ap1 expression in each mammalian species correlates with the duration of its preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence.
Topics: Animals; Base Sequence; Blastocyst; Cell Proliferation; Conserved Sequence; Embryonic Development; Evolution, Molecular; Female; Gene Expression Regulation, Developmental; Human Embryonic Stem Cells; Humans; Mammals; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Promoter Regions, Genetic; Protein Isoforms; Protein Kinases; Retroelements; Tumor Suppressor Proteins; Mice
PubMed: 34644528
DOI: 10.1016/j.cell.2021.09.021 -
International Journal of Molecular... Aug 2020The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies to restore the energy balance. Therefore, the concept of activating brown... (Review)
Review
The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies to restore the energy balance. Therefore, the concept of activating brown adipose tissue (BAT) in order to increase energy expenditure has been revived. In mammals, two developmentally distinct types of brown adipocytes exist; the classical or constitutive BAT that arises during embryogenesis, and the beige adipose tissue that is recruited postnatally within white adipose tissue (WAT) in the process called browning. Research of recent years has significantly increased our understanding of the mechanisms involved in BAT activation and WAT browning. They also allowed for the identification of critical molecules and critical steps of both processes and, therefore, many new therapeutic targets. Several non-pharmacological approaches, as well as chemical compounds aiming at the induction of WAT browning and BAT activation, have been tested in vitro as well as in animal models of genetically determined and/or diet-induced obesity. The therapeutic potential of some of these strategies has also been tested in humans. In this review, we summarize present concepts regarding potential therapeutic targets in the process of BAT activation and WAT browning and available strategies aiming at them.
Topics: Adipose Tissue, Beige; Adipose Tissue, Brown; Animals; Diet; Energy Metabolism; Gene Expression Regulation; Gene Regulatory Networks; Humans; Obesity
PubMed: 32872317
DOI: 10.3390/ijms21176241 -
Annual Review of Clinical Psychology May 2023Acculturation and psychopathology are linked in integrated, interactional, intersectional, and dynamic ways that span different types of intercultural contact, levels of... (Review)
Review
Acculturation and psychopathology are linked in integrated, interactional, intersectional, and dynamic ways that span different types of intercultural contact, levels of analysis, timescales, and contexts. A developmental psychopathology approach can be useful to explain why, how, and what about psychological acculturation results in later adaptation or maladaptation for acculturating youth and adults. This review applies a conceptual model of acculturation and developmental psychopathology to a widely used framework of acculturation variables producing an Integrated Process Framework of Acculturation Variables (IP-FAV). This new comprehensive framework depicts major predisposing acculturation conditions (why) as well as acculturation orientations and processes (how) that result in adaptation and maladaptation across the life span (what). The IP-FAV is unique in that it integrates both proximal and remote acculturation variables and explicates key acculturation processes to inform research, practice, and policy.
Topics: Acculturation; Mental Disorders; Psychopathology; United States; Humans; Child
PubMed: 36854286
DOI: 10.1146/annurev-clinpsy-080921-080622 -
Journal of Biosciences 2020Post-translational modification (PTM) in histone proteins is a covalent modification which mainly consists of methylation, phosphorylation, acetylation, ubiquitylation,... (Review)
Review
Post-translational modification (PTM) in histone proteins is a covalent modification which mainly consists of methylation, phosphorylation, acetylation, ubiquitylation, SUMOylation, glycosylation, and ADP-ribosylation. PTMs have fundamental roles in chromatin structure and function. Histone modifications have also been known as epigenetic markers. The PTMs that have taken place in histone proteins can affect gene expression by altering chromatin structure. Histone modifications act in varied biological processes such as transcriptional activation/inactivation, chromosome packaging, mitosis, meiosis, apoptosis, and DNA damage/repair. Defects in the PTMs pathway have been associated with the occurrence and progression of various human diseases, such as cancer, heart failure, autoimmune diseases, and neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and Huntington's disease. Histone modifications are reversible and used as potential targets for cancer therapy and prevention. Recent different histone PTMs have key roles in cancer cells since it has been shown that histone PTMs markers in cancers are acetylation, methylation, phosphorylation, and ubiquitylation. In this review, we have summarized the six most studied histone modifications and have examined the role of these modifications in the development of cancer.
Topics: Acetylation; Developmental Disabilities; Glycosylation; Histone Code; Histones; Humans; Nervous System Diseases; Phosphorylation; Protein Processing, Post-Translational; Ubiquitination
PubMed: 33184251
DOI: No ID Found -
BMC Biology Feb 2023Skeletal muscle development is a multistep process whose understanding is central in a broad range of fields and applications, from the potential medical value to human...
BACKGROUND
Skeletal muscle development is a multistep process whose understanding is central in a broad range of fields and applications, from the potential medical value to human society, to its economic value associated with improvement of agricultural animals. Skeletal muscle initiates in the somites, with muscle precursor cells generated in the dermomyotome and dermomyotome-derived myotome before muscle differentiation ensues, a developmentally regulated process that is well characterized in model organisms. However, the regulation of skeletal muscle ontogeny during embryonic development remains poorly defined in farm animals, for instance in pig. Here, we profiled gene expression and chromatin accessibility in developing pig somites and myotomes at single-cell resolution.
RESULTS
We identified myogenic cells and other cell types and constructed a differentiation trajectory of pig skeletal muscle ontogeny. Along this trajectory, the dynamic changes in gene expression and chromatin accessibility coincided with the activities of distinct cell type-specific transcription factors. Some novel genes upregulated along the differentiation trajectory showed higher expression levels in muscular dystrophy mice than that in healthy mice, suggesting their involvement in myogenesis. Integrative analysis of chromatin accessibility, gene expression data, and in vitro experiments identified EGR1 and RHOB as critical regulators of pig embryonic myogenesis.
CONCLUSIONS
Collectively, our results enhance our understanding of the molecular and cellular dynamics in pig embryonic myogenesis and offer a high-quality resource for the further study of pig skeletal muscle development and human muscle disease.
Topics: Animals; Mice; Cell Differentiation; Chromatin; Chromatin Immunoprecipitation Sequencing; Gene Expression Regulation, Developmental; Muscle Development; Muscle, Skeletal; Single-Cell Analysis; Single-Cell Gene Expression Analysis; Swine
PubMed: 36726129
DOI: 10.1186/s12915-023-01519-z -
Biophysical Journal Oct 2021The last decade has seen a major expansion in development of live biosensors, the tools needed to genetically encode them into model organisms, and the microscopic... (Review)
Review
The last decade has seen a major expansion in development of live biosensors, the tools needed to genetically encode them into model organisms, and the microscopic techniques used to visualize them. When combined, these offer us powerful tools with which to make fundamental discoveries about complex biological processes. In this review, we summarize the availability of biosensors to visualize an essential cellular process, the cell cycle, and the techniques for single-cell tracking and quantification of these reporters. We also highlight studies investigating the connection of cellular behavior to the cell cycle, particularly through live imaging, and anticipate exciting discoveries with the combination of these technologies in developmental contexts.
Topics: Biosensing Techniques; Cell Cycle; Cell Tracking
PubMed: 33964274
DOI: 10.1016/j.bpj.2021.04.035 -
Cellular and Molecular Life Sciences :... Dec 2021Zebrafish have emerged as a major model organism to study vertebrate reproduction due to their high fecundity and external development of eggs and embryos. The... (Review)
Review
Zebrafish have emerged as a major model organism to study vertebrate reproduction due to their high fecundity and external development of eggs and embryos. The mechanisms through which zebrafish determine their sex have come under extensive investigation, as they lack a definite sex-determining chromosome and appear to have a highly complex method of sex determination. Single-gene mutagenesis has been employed to isolate the function of genes that determine zebrafish sex and regulate sex-specific differentiation, and to explore the interactions of genes that promote female or male sexual fate. In this review, we focus on recent advances in understanding of the mechanisms, including genetic and environmental factors, governing zebrafish sex development with comparisons to gene functions in other species to highlight conserved and potentially species-specific mechanisms for specifying and maintaining sexual fate.
Topics: Animals; Female; Germ Cells; Male; Protein Processing, Post-Translational; RNA; Sex Determination Processes; Sex Differentiation; Zebrafish
PubMed: 34936027
DOI: 10.1007/s00018-021-04066-4 -
Antioxidants & Redox Signaling Apr 2020The geological record shows that as atmospheric O levels increased, it concomitantly coincided with the evolution of metazoans. More complex, higher organisms contain a... (Review)
Review
The geological record shows that as atmospheric O levels increased, it concomitantly coincided with the evolution of metazoans. More complex, higher organisms contain a more cysteine-rich proteome, potentially as a means to regulate homeostatic responses in a more O-rich environment. Regulation of redox-sensitive processes to control development is likely to be evolutionarily conserved. During early embryonic development, the conceptus is exposed to varying levels of O. Oxygen and redox-sensitive elements can be regulated to promote normal development, defined as changes to cellular mass, morphology, biochemistry, and function, suggesting that O is a developmental morphogen. During periods of O fluctuation, embryos are "reprogrammed," on the genomic and metabolic levels. Reprogramming imparts changes to particular redox couples (nodes) that would support specific post-translational modifications (PTMs), targeting the cysteine proteome to regulate protein function and development. Major developmental events such as stem cell expansion, proliferation, differentiation, migration, and cell fate decisions are controlled through oxidative PTMs of cysteine-based redox nodes. As such, timely coordinated redox regulation of these events yields normal developmental outcomes and viable species reproduction. Disruption of normal redox signaling can produce adverse developmental outcomes. Furthering our understanding of the redox-sensitive processes/pathways, the nature of the regulatory PTMs involved in development and periods of activation/sensitivity to specific developmental pathways would greatly support the theory of redox regulation of development, and would also provide rationale and direction to more fully comprehend poor developmental outcomes, such as dysmorphogenesis, functional deficits, and preterm embryonic death.
Topics: Animals; Biological Evolution; Environment; Humans; Oxidation-Reduction; Oxidative Stress; Oxygen; Protein Processing, Post-Translational
PubMed: 31891515
DOI: 10.1089/ars.2019.7976