scholarly journals Functional Requirement for Histone Deacetylase 1 in Caenorhabditis elegans Gonadogenesis

2002 ◽  
Vol 22 (9) ◽  
pp. 3024-3034 ◽  
Author(s):  
Pascale Dufourcq ◽  
Martin Victor ◽  
Frédérique Gay ◽  
Dominica Calvo ◽  
Jonathan Hodgkin ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Notch Signaling Pathway ◽  
Transcriptional Repressors ◽  
Vulval Development ◽  
C Elegans ◽  
Histone Deacetylase 1 ◽  
Multicellular Organisms

ABSTRACT Histone acetylation and deacetylation have been implicated in the regulation of gene expression. Molecular studies have shown that histone deacetylases (HDACs) function as transcriptional repressors. However, very little is known about their roles during development in multicellular organisms. We previously demonstrated that inhibition of maternal and zygotic expression of histone deacetylase 1 (HDA-1) causes embryonic lethality in Caenorhabditis elegans. Here, we report the identification of an hda-1 genetic mutant which has also been called a gon-10 mutant (for gonadogenesis defective 10) and show that loss of HDA-1 zygotic expression results in specific postembryonic defects in gonadogenesis and vulval development. We provide evidence that the lag-2 gene, which plays a role in gonadogenesis and vulval development and encodes a Notch ligand, is derepressed in gon-10 animals, suggesting that lag-2 may be a target of HDA-1. Our findings reveal a novel and specific function for the ubiquitously expressed HDA-1 in C. elegans gonadogenesis and place hda-1 in the Notch signaling pathway.

scholarly journals Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors, LET-418, SIN-3, and SPR-1 in Caenorhabditis elegans embryonic development

2020 ◽  
Author(s):  
Yukihiro Kubota ◽  
Yuto Ohnishi ◽  
Tasuku Hamasaki ◽  
Gen Yasui ◽  
Natsumi Ota ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Histone Deacetylases ◽  
Class I ◽  
Biological Processes ◽  
Nucleosome Remodeling ◽  
C Elegans ◽  
Histone Deacetylase 1 ◽  
Genome Wide ◽  
Sin3 Complex

AbstractHistone deacetylases (HDACs) are divided into four classes. Class-I HDAC, HDAC-1 forms three types of complexes, namely the Nucleosome Remodeling Deacetylase complex, the Sin3 complex, and the CoREST complex, with specific corepressor component Mi2/CHD-3, Sin3, and RCOR1 in human, respectively. The functions of these HDAC-1 complexes are regulated by their corepressors, however, their exact mechanistic roles in several biological processes remain unexplored, such as in embryonic development. Here, we report that each of the corepressors, LET-418, SIN-3, and SPR-1, the homologous of Mi2, Sin3, and RCOR1, respectively, were expressed throughout Caenorhabditis elegans embryonic development and served essential roles in the process. Moreover, genetic analysis suggested that three pathways (i.e., LET-418– SIN-3–SPR-1, SIN-3–SPR-1, and LET-418) participated in embryonic development. Our terminal-phenotype observations of single mutants of each corepressor implied that LET-418, SIN-3, and SPR-1 played similar roles in promoting advancement to the middle and late embryonic stages. Genome-wide comparative-transcriptome analysis indicated that 47.5% and 42.3% of genes were commonly increased and decreased in sin-3 and spr-1 mutants, respectively. These results suggest that among the three pathways studied, the SIN-3–SPR-1 pathway mainly serves to regulate embryonic development. Comparative-Gene Ontology analysis indicated that these three pathways played overlapping and distinct roles in regulating C. elegans embryonic development.

scholarly journals Neuroprotection by Histone Deacetylase-Related Protein

2006 ◽  
Vol 26 (9) ◽  
pp. 3550-3564 ◽  
Author(s):  
Brad E. Morrison ◽  
Nazanin Majdzadeh ◽  
Xiaoguang Zhang ◽  
Aaron Lyles ◽  
Rhonda Bassel-Duby ◽  
...  
Keyword(s):  
Cell Death ◽  
Histone Deacetylase ◽  
Neuronal Death ◽  
Histone Deacetylases ◽  
Essential Feature ◽  
Gene Promoter ◽  
Related Protein ◽  
Phosphatidylinositol 3 Kinase ◽  
Histone Deacetylase 1 ◽  
H3 Acetylation

ABSTRACT The expression of histone deacetylase-related protein (HDRP) is reduced in neurons undergoing apoptosis. Forced reduction of HDRP expression in healthy neurons by treatment with antisense oligonucleotides also induces cell death. Likewise, neurons cultured from mice lacking HDRP are more vulnerable to cell death. Adenovirally mediated expression of HDRP prevents neuronal death, showing that HDRP is a neuroprotective protein. Neuroprotection by forced expression of HDRP is not accompanied by activation of the phosphatidylinositol 3-kinase-Akt or Raf-MEK-ERK signaling pathway, and treatment with pharmacological inhibitors of these pathways fails to inhibit the neuroprotection by HDRP. Stimulation of c-Jun phosphorylation and expression, an essential feature of neuronal death, is prevented by HDRP. We found that HDRP associates with c-Jun N-terminal kinase (JNK) and inhibits its activity, thus explaining the inhibition of c-Jun phosphorylation by HDRP. HDRP also interacts with histone deacetylase 1 (HDAC1) and recruits it to the c-Jun gene promoter, resulting in an inhibition of histone H3 acetylation at the c-Jun promoter. Although HDRP lacks intrinsic deacetylase activity, treatment with pharmacological inhibitors of histone deacetylases induces apoptosis even in the presence of ectopically expressed HDRP, underscoring the importance of c-Jun promoter deacetylation by HDRP-HDAC1 in HDRP-mediated neuroprotection. Our results suggest that neuroprotection by HDRP is mediated by the inhibition of c-Jun through its interaction with JNK and HDAC1.

A Dynamic Body Model of the NematodeC. eleganswith Neural Oscillators

2005 ◽  
Vol 17 (3) ◽  
pp. 318-326 ◽  
Author(s):  
Michiyo Suzuki ◽  
◽  
Takeshi Goto ◽  
Toshio Tsuji ◽  
Hisao Ohtake ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Motor Control ◽  
Caenorhabditis Elegans ◽  
Neural Circuit ◽  
Rhythmic Movement ◽  
Circuit Model ◽  
Neural Oscillators ◽  
C Elegans ◽  
Body Model ◽  
Multicellular Organisms

The nematode <I>Caenorhabditis elegans (C. elegans)</I>, a relatively simple organism in structure, is one of the most well-studied multicellular organisms. We developed a <I>virtual C. elegans</I> based on the actual organism to analyze motor control. We propose a dynamic body model, including muscles, controlled by a neural circuit model based on the actual nematode. The model uses neural oscillators to generate rhythmic movement. Computer simulation confirmed that the <I>virtual C. elegans</I> realizes motor control similar qualitatively to that of the actual organism. Specified classes of neurons are killed in the neural circuit model corresponding to actual <I>unc</I> mutants, demonstrating that resulting movement of the <I>virtual C. elegans</I> resembles that of actual mutants.

scholarly journals Regulation of the mitosis/meiosis decision in the Caenorhabditis elegans germline

2003 ◽  
Vol 358 (1436) ◽  
pp. 1359-1362 ◽  
Author(s):  
Sarah L. Crittenden ◽  
Christian R. Eckmann ◽  
Liaoteng Wang ◽  
David S. Bernstein ◽  
Marvin Wickens ◽  
...  
Keyword(s):  
Stem Cells ◽  
Caenorhabditis Elegans ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Germline Stem Cells ◽  
Puf Proteins ◽  
C Elegans ◽  
Transcriptional Regulatory ◽  
Mitotic Proliferation ◽  
Multicellular Organisms

During the development of multicellular organisms, the processes of growth and differentiation are kept in balance to generate and maintain tissues and organs of the correct size, shape and cellular composition. We have investigated the molecular controls of growth and differentiation in the Caenorhabditis elegans germline. A single somatic cell, called the distal tip cell, promotes mitotic proliferation in the adjacent germline by GLP–1/Notch signalling. Within the germline, the decisions between mitosis and meiosis and between spermatogenesis and oogenesis are controlled by a group of conserved RNA regulators. FBF, a member of the PUF (for Pumilio and FBF) family of RNA–binding proteins, promotes mitosis by repressing gld–1 mRNA activity; the GLD–1, GLD–2, GLD–3 and NOS–3 proteins promote entry into meiosis by regulating mRNAs that remain unknown. The regulatory balance between opposing FBF and GLD activities is crucial for controlling the extent of germline proliferation. PUF proteins regulate germline stem cells in both Drosophila and C. elegans and are localized to germline stem cells of the mammalian testis. Therefore, this post–transcriptional regulatory switch may be an ancient mechanism for controlling maintenance of stem cells versus differentiation.

scholarly journals The functional repertoire encoded within the native microbiome of the model nematode Caenorhabditis elegans

2019 ◽  
Author(s):  
Johannes Zimmermann ◽  
Nancy Obeng ◽  
Wentao Yang ◽  
Barbara Pees ◽  
Carola Petersen ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Integrative Approach ◽  
Metabolic Modelling ◽  
Bacterial Physiology ◽  
C Elegans ◽  
Pyruvate Fermentation ◽  
Bacterial Microbiome ◽  
Multicellular Organisms ◽  
Taxonomic Characterization

AbstractThe microbiome is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of the bacterial associates. In order to bridge this knowledge gap, we here analyzed the metabolic competences of the native microbiome of the model nematode Caenorhabditis elegans. We integrated whole genome sequences of 77 bacterial microbiome members with metabolic modelling and experimental characterization of bacterial physiology. We found that, as a community, the microbiome can synthesize all essential nutrients for C. elegans. Both metabolic models and experimental analyses further revealed that nutrient context can influence how bacteria interact within the microbiome. We identified key bacterial traits that are likely to influence the microbe’s ability to colonize C. elegans (e.g., pyruvate fermentation to acetoin) and the resulting effects on nematode fitness (e.g., hydroxyproline degradation). Considering that the microbiome is usually neglected in the comprehensive research on this nematode, the resource presented here will help our understanding of C. elegans biology in a more natural context. Our integrative approach moreover provides a novel, general framework to dissect microbiome-mediated functions.

scholarly journals Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis

2020 ◽  
Vol 21 (22) ◽  
pp. 8460
Author(s):  
Min Young Kim ◽  
Bowen Yan ◽  
Suming Huang ◽  
Yi Qiu
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Gene Activation ◽  
Bhlh Transcription Factor ◽  
Nucleosome Remodeling ◽  
Hdac Activity ◽  
Histone Deacetylase 1

Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. Class I deacetylase HDAC1/2 often associates with repressor complexes, such as Sin3 (Switch Independent 3), NuRD (Nucleosome remodeling and deacetylase) and CoREST (Corepressor of RE1 silencing transcription factor) complexes. It has been shown that HDAC1 interacts with and modulates all essential transcription factors for erythropoiesis. During erythropoiesis, histone deacetylase activity is dramatically reduced. Consistently, inhibition of HDAC activity promotes erythroid differentiation. The reduction of HDAC activity not only results in the activation of transcription activators such as GATA-1 (GATA-binding factor 1), TAL1 (TAL BHLH Transcription Factor 1) and KLF1 (Krüpple-like factor 1), but also represses transcription repressors such as PU.1 (Putative oncogene Spi-1). The reduction of histone deacetylase activity is mainly through HDAC1 acetylation that attenuates HDAC1 activity and trans-repress HDAC2 activity through dimerization with HDAC1. Therefore, the acetylation of HDAC1 can convert the corepressor complex to an activator complex for gene activation. HDAC1 also can deacetylate non-histone proteins that play a role on erythropoiesis, therefore adds another layer of gene regulation through HDAC1. Clinically, it has been shown HDACi can reactivate fetal globin in adult erythroid cells. This review will cover the up to date research on the role of HDAC1 in modulating key transcription factors for erythropoiesis and its clinical relevance.

scholarly journals Caenorhabditis elegans FOS-1 and JUN-1 Regulateplc-1Expression in the Spermatheca to Control Ovulation

2009 ◽  
Vol 20 (17) ◽  
pp. 3888-3895 ◽  
Author(s):  
Susan M. Hiatt ◽  
Holli M. Duren ◽  
Y. John Shyu ◽  
Ronald E. Ellis ◽  
Naoki Hisamoto ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Chromatin Remodeling ◽  
Genetic Interactions ◽  
Inositol Triphosphate ◽  
Activator Protein 1 ◽  
Specific Expression ◽  
Vulval Development ◽  
C Elegans ◽  
Physiological Processes ◽  
Rate Limiting

Fos and Jun are components of activator protein-1 (AP-1) and play crucial roles in the regulation of many cellular, developmental, and physiological processes. Caenorhabditis elegans fos-1 has been shown to act in uterine and vulval development. Here, we provide evidence that C. elegans fos-1 and jun-1 control ovulation, a tightly regulated rhythmic program in animals. Knockdown of fos-1 or jun-1 blocks dilation of the distal spermathecal valve, a critical step for the entry of mature oocytes into the spermatheca for fertilization. Furthermore, fos-1 and jun-1 regulate the spermathecal-specific expression of plc-1, a gene that encodes a phospholipase C (PLC) isozyme that is rate-limiting for inositol triphosphate production and ovulation, and overexpression of PLC-1 rescues the ovulation defect in fos-1(RNAi) worms. Unlike fos-1, regulation of ovulation by jun-1 requires genetic interactions with eri-1 and lin-15B, which are involved in the RNA interference pathway and chromatin remodeling, respectively. At least two isoforms of jun-1 are coexpressed with fos-1b in the spermatheca, and different AP-1 dimers formed between these isoforms have distinct effects on the activation of a reporter gene. These findings uncover a novel role for FOS-1 and JUN-1 in the reproductive system and establish C. elegans as a model for studying AP-1 dimerization.

scholarly journals LET-711, the Caenorhabditis elegans NOT1 Ortholog, Is Required for Spindle Positioning and Regulation of Microtubule Length in Embryos

2006 ◽  
Vol 17 (11) ◽  
pp. 4911-4924 ◽  
Author(s):  
Leah R. DeBella ◽  
Adam Hayashi ◽  
Lesilee S. Rose
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Regulation Of Gene Expression ◽  
Early Embryo ◽  
Cell Cortex ◽  
Loss Of Function ◽  
Wild Type ◽  
Spindle Positioning ◽  
C Elegans ◽  
Associated Proteins

Spindle positioning is essential for the segregation of cell fate determinants during asymmetric division, as well as for proper cellular arrangements during development. In Caenorhabditis elegans embryos, spindle positioning depends on interactions between the astral microtubules and the cell cortex. Here we show that let-711 is required for spindle positioning in the early embryo. Strong loss of let-711 function leads to sterility, whereas partial loss of function results in embryos with defects in the centration and rotation movements that position the first mitotic spindle. let-711 mutant embryos have longer microtubules that are more cold-stable than in wild type, a phenotype opposite to the short microtubule phenotype caused by mutations in the C. elegans XMAP215 homolog ZYG-9. Simultaneous reduction of both ZYG-9 and LET-711 can rescue the centration and rotation defects of both single mutants. let-711 mutant embryos also have larger than wild-type centrosomes at which higher levels of ZYG-9 accumulate compared with wild type. Molecular identification of LET-711 shows it to be an ortholog of NOT1, the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels in yeast, flies, and mammals. We therefore propose that LET-711 inhibits the expression of ZYG-9 and potentially other centrosome-associated proteins, in order to maintain normal centrosome size and microtubule dynamics during early embryonic divisions.

scholarly journals Protein Kinase CK2 Regulates the Dimerization of Histone Deacetylase 1 (HDAC1) and HDAC2 during Mitosis

2013 ◽  
Vol 288 (23) ◽  
pp. 16518-16528 ◽  
Author(s):  
Dilshad H. Khan ◽  
Shihua He ◽  
Jenny Yu ◽  
Stefan Winter ◽  
Wenguang Cao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Histone Deacetylase ◽  
Chromatin Remodeling ◽  
Protein Kinase Ck2 ◽  
Regulation Of Gene Expression ◽  
Protein Acetylation ◽  
Histone Deacetylase 1 ◽  
Interphase Cells ◽  
Kinase Ck2 ◽  
Inhibition Studies

Histone deacetylase 1 (HDAC1) and HDAC2 are components of corepressor complexes that are involved in chromatin remodeling and regulation of gene expression by regulating dynamic protein acetylation. HDAC1 and -2 form homo- and heterodimers, and their activity is dependent upon dimer formation. Phosphorylation of HDAC1 and/or HDAC2 in interphase cells is required for the formation of HDAC corepressor complexes. In this study, we show that during mitosis, HDAC2 and, to a lesser extent, HDAC1 phosphorylation levels dramatically increase. When HDAC1 and -2 are displaced from the chromosome during metaphase, they dissociate from each other, but each enzyme remains in association with components of the HDAC corepressor complexes Sin3, NuRD, and CoREST as homodimers. Enzyme inhibition studies and mutational analyses demonstrated that protein kinase CK2-catalyzed phosphorylation of HDAC1 and -2 is crucial for the dissociation of these two enzymes. These results suggest that corepressor complexes, including HDAC1 or HDAC2 homodimers, might target different cellular proteins during mitosis.

scholarly journals Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors LET-418, SIN-3, and SPR-1 in Caenorhabditis elegans embryonic development

2021 ◽  
Author(s):  
Yukihiro Kubota ◽  
Yuto Ohnishi ◽  
Tasuku Hamasaki ◽  
Gen Yasui ◽  
Natsumi Ota ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Embryonic Development ◽  
Histone Deacetylase ◽  
Genetic Interactions ◽  
Class I ◽  
Specific Cell ◽  
Nucleosome Remodeling ◽  
Expression Levels ◽  
C Elegans ◽  
Functional Relationships

AbstractBackgroundHistone deacetylase (HDAC)-1, a Class-I HDAC family member, forms three types of complexes, the nucleosome remodeling deacetylase, Sin3, and CoREST complexes with the specific corepressor components chromodomain-helicase-DNA-binding protein 3 (Mi2/CHD-3), Sin3, and REST corepressor 1 (RCOR1), respectively, in humans.ObjectiveTo elucidate the functional relationships among the three transcriptional corepressors during embryogenesis.MethodsThe activities of HDA-1, LET-418, SIN-3, and SPR-1, the homologs of HDAC-1, Mi2, Sin3, and RCOR1 inCaenorhabditis elegansduring embryogenesis were investigated through measurement of relative mRNA expression levels and embryonic lethality given either gene knockdown or deletion. Additionally, the terminal phenotypes of each knockdown and mutant embryo were observed using a differential-interference contrast microscope. Finally, the functional relationships among the three corepressors were examined through genetic interactions and transcriptome analyses.ResultsHere, we report that each of the corepressors LET-418, SIN-3, and SPR-1 are expressed and have essential roles inC. elegansembryonic development. Our terminal phenotype observations of single mutants further implied that LET-418, SIN-3, and SPR-1 play similar roles in promoting advancement to the middle and late embryonic stages. Combined analysis of genetic interactions and gene ontology of these corepressors indicate a prominent overlapping role among SIN-3, SPR-1, and LET-418 and between SIN-3 and SPR-1.ConclusionOur findings suggest that the class-I HDAC-1 corepressors LET-418, SIN-3, and SPR-1 may cooperatively regulate the expression levels of some genes duringC. elegansembryogenesis or may have some similar roles but functioning independently within a specific cell.

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