scholarly journals Compensatory replacement of the BigH1 variant histone by canonical H1 supports normal embryonic development in Drosophila

2019 ◽  
Author(s):  
Kaili K. Li ◽  
Dongsheng Han ◽  
Fang Chen ◽  
Ruihao Li ◽  
Bing-Rui Zhou ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Histone H1 ◽  
Histone Variants ◽  
Linker Histone ◽  
Chromatin State ◽  
Biological Functions ◽  
Developmental Context ◽  
Early Embryos ◽  
Essential Function ◽  
Normal Embryonic Development

SummaryHistone variants carry specific functions in addition to those fulfilled by their canonical counterparts. Variants of the linker Histone H1 are prevalent in vertebrates and based on the pattern of their expression, many are presumed to function during germline and the earliest zygotic stages of development. While the existence of multiple H1 variants has hampered their study in vertebrates, a single variant, BigH1, was identified in Drosophila, promising to accelerate our understanding of the biological functions of H1 and H1 variants. Here we uncovered evidence for a compensatory activity that loads maternal H1 onto BigH1-devoid chromatin. Remarkably, this H1-based chromatin state is fully functional in supporting normal embryonic development, suggesting that H1 carries the essential function of the BigH1 molecule under the same developmental context. In addition, we discovered that this compensatory replacement of BigH1 with H1 might be limited to rapidly cycling cells in early embryos.

scholarly journals Label-Free Mass Spectrometry-Based Quantification of Linker Histone H1 Variants in Clinical Samples

2020 ◽  
Vol 21 (19) ◽  
pp. 7330
Author(s):  
Roberta Noberini ◽  
Cristina Morales Torres ◽  
Evelyn Oliva Savoia ◽  
Stefania Brandini ◽  
Maria Giovanna Jodice ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Histone H1 ◽  
Histone Variants ◽  
Linker Histone ◽  
Clinical Samples ◽  
Label Free ◽  
Complex Samples ◽  
Linker Histone H1 ◽  
Ideal Tool ◽  
Free Quantification

Epigenetic aberrations have been recognized as important contributors to cancer onset and development, and increasing evidence suggests that linker histone H1 variants may serve as biomarkers useful for patient stratification, as well as play an important role as drivers in cancer. Although traditionally histone H1 levels have been studied using antibody-based methods and RNA expression, these approaches suffer from limitations. Mass spectrometry (MS)-based proteomics represents the ideal tool to accurately quantify relative changes in protein abundance within complex samples. In this study, we used a label-free quantification approach to simultaneously analyze all somatic histone H1 variants in clinical samples and verified its applicability to laser micro-dissected tissue areas containing as low as 1000 cells. We then applied it to breast cancer patient samples, identifying differences in linker histone variants patters in primary triple-negative breast tumors with and without relapse after chemotherapy. This study highlights how label-free quantitation by MS is a valuable option to accurately quantitate histone H1 levels in different types of clinical samples, including very low-abundance patient tissues.

The C. elegans septin genes, unc-59 and unc-61, are required for normal postembryonic cytokineses and morphogenesis but have no essential function in embryogenesis

2000 ◽  
Vol 113 (21) ◽  
pp. 3825-3837 ◽  
Author(s):  
T.Q. Nguyen ◽  
H. Sawa ◽  
H. Okano ◽  
J.G. White
Keyword(s):  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Sensory Neurons ◽  
Leading Edge ◽  
The Other ◽  
Male Tail ◽  
Genomic Database ◽  
C Elegans ◽  
Essential Function ◽  
Normal Embryonic Development

Septins have been shown to play important roles in cytokinesis in diverse organisms ranging from yeast to mammals. In this study, we show that both the unc-59 and unc-61 loci encode Caenorhabditis elegans septins. Genomic database searches indicate that unc-59 and unc-61 are probably the only septin genes in the C. elegans genome. UNC-59 and UNC-61 localize to the leading edge of cleavage furrows and eventually reside at the midbody. Analysis of unc-59 and unc-61 mutants revealed that each septin requires the presence of the other for localization to the cytokinetic furrow. Surprisingly, unc-59 and unc-61 mutants generally have normal embryonic development; however, defects were observed in post-embryonic development affecting the morphogenesis of the vulva, male tail, gonad, and sensory neurons. These defects can be at least partially attributed to failures in post-embryonic cytokineses although our data also suggest other possible roles for septins. unc-59 and unc-61 double mutants show similar defects to each of the single mutants.

Abstract 199: Distinctive Roles of Linker Histone H1 Variants in the Hypertrophic Response of Cardiomyocytes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Michelle S Parvatiyar ◽  
Timothy D Lopez ◽  
Sarah Franklin ◽  
Thomas M Vondriska
Keyword(s):  
Histone H1 ◽  
Histone Variants ◽  
Linker Histone ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels ◽  
Hypertrophic Response ◽  
Linker Histone H1 ◽  
Knock Down

Heart failure results when cardiac output is insufficient to meet physiological requirements and is often preceded by development of cardiomyocyte hypertrophy. As cardiac myocytes respond to hypertrophic stresses they re-express developmentally important genes, normally senescent in the adult. The chromatin structural events underlying this “fetal gene program” are unknown. We previously showed by proteomics that histones, components of the chromatin protein functional unit, the nucleosome, are altered during hypertrophic and failing phases of pressure overload in mouse: linker histone variants H1.2 and H1.5 decreased in hypertrophied myocardium while H1.0 increased during the transition to failure. The linker histone H1 family influences higher order chromatin structure and gene expression, although the role of this family in the heart is unknown. To assess the role of linker histones in hypertrophy, neonatal rat ventricular cardiomyocytes (NRVMs) were transfected with siRNAs individually targeting six H1 variants. Loss of H1.3 and H1.4 respectively induced a significant 26.1% (76 of 90) and 13.5% (80 of 94) increase in cell size area (µm2). A role of H1 in the hypertrophic response is evidenced by its influence on myosin heavy chain (MHC) mRNA expression. Knock-down of individual H1 variants significantly altered the MHC isoform ratio: loss of H1.3 increased α-MHC levels 1.5 fold and decreased β-MHC 1.6 fold while H1.5 depletion decreased α-MHC 2.5 fold. Both H1.3 and H1.4 knock-down increased atrial natriuretic factor (ANF) 1.3 fold while H1.5 loss decreased ANF 6.2 fold shown by qRT-PCR. Treatment with hypertrophy-inducing agents Isoproterenol (1μM), Endothelin (2nM) or Phenylephrine (10μM), reduced H1 mRNA levels however with subtle effects on protein abundance. To evaluate whether H1 loss shifted NRVM nuclei from a predominantly heterochromatic toward euchromatic state favoring gene accessibility we examined distinct histone markers of chromatin states. Histone H1.5 knock-down significantly decreased H3K9Me3 levels, a silencing mark associated with heterochromatin, 1.7 fold. Therefore we conclude that variants package distinctive regions of the genome and that H1.3 and H1.4 controls genes involved in the hypertrophic response.

scholarly journals Site-specific ubiquitylation acts as a regulator of linker histone H1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eva Höllmüller ◽  
Simon Geigges ◽  
Marie L. Niedermeier ◽  
Kai-Michael Kammer ◽  
Simon M. Kienle ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Histone H1 ◽  
Linker Histone ◽  
Active Chromatin ◽  
Site Specific ◽  
Linker Histone H1 ◽  
Fundamental Process ◽  
Core Histones ◽  
Wide Scale

AbstractDecoding the role of histone posttranslational modifications (PTMs) is key to understand the fundamental process of epigenetic regulation. This is well studied for PTMs of core histones but not for linker histone H1 in general and its ubiquitylation in particular due to a lack of proper tools. Here, we report on the chemical synthesis of site-specifically mono-ubiquitylated H1.2 and identify its ubiquitin-dependent interactome on a proteome-wide scale. We show that site-specific ubiquitylation of H1 at position K64 modulates interactions with deubiquitylating enzymes and the deacetylase SIRT1. Moreover, it affects H1-dependent chromatosome assembly and phase separation resulting in a more open chromatosome conformation generally associated with a transcriptionally active chromatin state. In summary, we propose that site-specific ubiquitylation plays a general regulatory role for linker histone H1.

scholarly journals Reproductive biology, embryonic development and matrotrophy in the phylactolaemate bryozoan Plumatella casmiana

2021 ◽  
Author(s):  
Julian Bibermair ◽  
Andrew N. Ostrovsky ◽  
Andreas Wanninger ◽  
Thomas Schwaha
Keyword(s):  
Embryonic Development ◽  
Embryo Sac ◽  
The Body ◽  
Transcellular Transport ◽  
Cell Contacts ◽  
Transmission Electron ◽  
Distal Side ◽  
Early Embryos ◽  
Mesoderm Formation ◽  
Cytoplasmic Processes

AbstractBryozoa is a phylum of aquatic, colonial suspension-feeders within the Lophotrochozoa. In the Phylactolaemata embryonic development occurs in an internal brood sac on the body wall accompanied by extraembryonic nutrition. Owing to previous contradictive descriptions, many aspects of their sexual reproduction require restudy. Consequently, this study analyses embryogenesis of the freshwater bryozoan Plumatella casmiana by serial sections, 3D reconstruction and transmission electron microscopy. Early embryos cleave and soon develop into blastulae with a small central cavity. The mesoderm forms by delamination starting from the distal side towards the proximal end. In later embryos two polypides form on the posterior side that ultimately will be covered by a ciliated mantle in the larva. Embryos increase in size during development and form temporary cell contacts to the embryo sac. Mesodermal cells of the embryo sac show signs of transcellular transport indicating that embryos are nourished by transferring nutrients from the maternal coelom towards the brood cavity. This study clarifies several details such as mesoderm formation and the onset of bud development. Embryos are connected to their respective embryo sacs by a variety of temporary cytoplasmic processes formed by both tissues during embryogenesis, including a ‘placental’ ring zone. Although ultrastructural data of these cell contacts are not entirely conclusive about their function, we suggest that embryos absorb nutrients via the entire surface. The close opposition of embryos to the embryo sac implies placentation as matrotrophic mode in phylactolaemate bryozoans, with embryo sacs acting as placental analogues.

scholarly journals Unfolded protein response triggers differential apoptotic mechanisms in ovaries and early embryos exposed to maternal type 1 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aslı Okan ◽  
Necdet Demir ◽  
Berna Sozen
Keyword(s):  
Embryonic Development ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Molecular Mechanisms ◽  
Early Embryonic Development ◽  
Unfolded Protein ◽  
Caspase 12 ◽  
Early Embryos ◽  
Protein Response

AbstractDiabetes mellitus (DM) has profound effects on the female mammalian reproductive system, and early embryonic development, reducing female reproductive outcomes and inducing developmental programming in utero. However, the underlying cellular and molecular mechanisms remain poorly defined. Accumulating evidence implicates endoplasmic reticulum (ER)-stress with maternal DM associated pathophysiology. Yet the direct pathologies and causal events leading to ovarian dysfunction and altered early embryonic development have not been determined. Here, using an in vivo mouse model of Type 1 DM and in vitro hyperglycaemia-exposure, we demonstrate the activation of ER-stress within adult ovarian tissue and pre-implantation embryos. In diabetic ovaries, we show that the unfolded protein response (UPR) triggers an apoptotic cascade by the co-activation of Caspase 12 and Cleaved Caspase 3 transducers. Whereas DM-exposed early embryos display differential ER-associated responses; by activating Chop in within embryonic precursors and Caspase 12 within placental precursors. Our results offer new insights for understanding the pathological effects of DM on mammalian ovarian function and early embryo development, providing new evidence of its mechanistic link with ER-stress in mice.

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