scholarly journals Stable C. elegans chromatin domains separate broadly expressed and developmentally regulated genes

2016 ◽  
Author(s):  
Kenneth J. Evans ◽  
Ni Huang ◽  
Przemyslaw Stempor ◽  
Michael A. Chesney ◽  
Thomas A. Down ◽  
...  

AbstractEukaryotic genomes are organized into domains of differing structure and activity. There is evidence that the domain organization of the genome regulates its activity, yet our understanding of domain properties and the factors that influence their formation is poor. Here we use chromatin state analyses in early embryos and L3 larvae to investigate genome domain organization and its regulation in C. elegans. At both stages we find that the genome is organized into extended chromatin domains of high or low gene activity defined by different subsets of states, and enriched for H3K36me3 or H3K27me3 respectively. The border regions between domains contain large intergenic regions and a high density of transcription factor binding, suggesting a role for transcription regulation in separating chromatin domains. Despite the differences in cell types, overall domain organization is remarkably similar in early embryos and L3 larvae, with conservation of 85% of domain border positions. Most genes in high activity domains are expressed in the germ line and broadly across cell types, whereas low activity domains are enriched for genes that are developmentally regulated. We find that domains are regulated by the germ line H3K36 methyltransferase MES-4 and that border regions show striking remodeling of H3K27me1, supporting roles for H3K36 and H3K27 methylation in regulating domain structure. Our analyses of C. elegans chromatin domain structure show that genes are organized by type into domains that have differing modes of regulation.Significance statementGenomes are organized into domains of different structure and activity, yet our understanding of their formation and regulation is poor. We show that C. elegans chromatin domain organization in early embryos and L3 larvae is remarkably similar despite the two developmental stages containing very different cell types. Chromatin domains separate genes into those with stable versus developmentally regulated expression. Analyses of chromatin domain structure suggest that transcription regulation and germ line chromatin regulation play roles in separating chromatin domains. Our results further our understanding of genome domain organization.

2016 ◽  
Vol 113 (45) ◽  
pp. E7020-E7029 ◽  
Author(s):  
Kenneth J. Evans ◽  
Ni Huang ◽  
Przemyslaw Stempor ◽  
Michael A. Chesney ◽  
Thomas A. Down ◽  
...  

Eukaryotic genomes are organized into domains of differing structure and activity. There is evidence that the domain organization of the genome regulates its activity, yet our understanding of domain properties and the factors that influence their formation is poor. Here, we use chromatin state analyses in early embryos and third-larval stage (L3) animals to investigate genome domain organization and its regulation in Caenorhabditis elegans. At both stages we find that the genome is organized into extended chromatin domains of high or low gene activity defined by different subsets of states, and enriched for H3K36me3 or H3K27me3, respectively. The border regions between domains contain large intergenic regions and a high density of transcription factor binding, suggesting a role for transcription regulation in separating chromatin domains. Despite the differences in cell types, overall domain organization is remarkably similar in early embryos and L3 larvae, with conservation of 85% of domain border positions. Most genes in high-activity domains are expressed in the germ line and broadly across cell types, whereas low-activity domains are enriched for genes that are developmentally regulated. We find that domains are regulated by the germ-line H3K36 methyltransferase MES-4 and that border regions show striking remodeling of H3K27me1, supporting roles for H3K36 and H3K27 methylation in regulating domain structure. Our analyses of C. elegans chromatin domain structure show that genes are organized by type into domains that have differing modes of regulation.


Tissue-specific animal cell genes are usually fully methylated in the germ line and become demethylated in those cell types in which they are expressed. To investigate this process, we inserted a methylated IgG K gene into fibroblasts and lymphocytes at various stages of development. The results show that this gene undergoes demethylation only in the mature lymphocytes and therefore suggest that the ability to demethylate a gene is developmentally regulated. These studies were supported by similar experiments using the rat Insulin I gene, and in this case it appears that the cis -acting elements that control demethylation may be different from those responsible for gene activation. The ability to demethylate the housekeeping gene APRT is also under developmental control, because this occurs only in embryonic cells, both in tissue culture and in transgenic mice.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Li-Wei Lee ◽  
Chi-Chang Lee ◽  
Chi-Ruei Huang ◽  
Szecheng J. Lo

Nucleolar size and appearance correlate with ribosome biogenesis and cellular activity. The mechanisms underlying changes in nucleolar appearance and regulation of nucleolar size that occur during differentiation and cell cycle progression are not well understood.Caenorhabditis elegansprovides a good model for studying these processes because of its small size and transparent body, well-characterized cell types and lineages, and because its cells display various sizes of nucleoli. This paper details the advantages of usingC. elegansto investigate features of the nucleolus during the organism's development by following dynamic changes in fibrillarin (FIB-1) in the cells of early embryos and aged worms. This paper also illustrates the involvement of thencl-1gene and other possible candidate genes in nucleolar-size control. Lastly, we summarize the ribosomal proteins involved in life span and innate immunity, and those homologous genes that correspond to human disorders of ribosomopathy.


2001 ◽  
Vol 12 (6) ◽  
pp. 1751-1764 ◽  
Author(s):  
Susan Strome ◽  
James Powers ◽  
Melanie Dunn ◽  
Kimberly Reese ◽  
Christian J. Malone ◽  
...  

γ-Tubulin is a ubiquitous and highly conserved component of centrosomes in eukaryotic cells. Genetic and biochemical studies have demonstrated that γ-tubulin functions as part of a complex to nucleate microtubule polymerization from centrosomes. We show that, as in other organisms, Caenorhabditis elegans γ-tubulin is concentrated in centrosomes. To study centrosome dynamics in embryos, we generated transgenic worms that express GFP::γ-tubulin or GFP::β-tubulin in the maternal germ line and early embryos. Multiphoton microscopy of embryos produced by these worms revealed the time course of daughter centrosome appearance and growth and the differential behavior of centrosomes destined for germ line and somatic blastomeres. To study the role of γ-tubulin in nucleation and organization of spindle microtubules, we used RNA interference (RNAi) to deplete C. elegansembryos of γ-tubulin. γ-Tubulin (RNAi) embryos failed in chromosome segregation, but surprisingly, they contained extensive microtubule arrays. Moderately affected embryos contained bipolar spindles with dense and long astral microtubule arrays but with poorly organized kinetochore and interpolar microtubules. Severely affected embryos contained collapsed spindles with numerous long astral microtubules. Our results suggest that γ-tubulin is not absolutely required for microtubule nucleation in C. elegans but is required for the normal organization and function of kinetochore and interpolar microtubules.


2007 ◽  
Vol 179 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Seung-Hwan Kim ◽  
Antonia H. Holway ◽  
Suzanne Wolff ◽  
Andrew Dillin ◽  
W. Matthew Michael

During early embryogenesis in Caenorhabditis elegans, the ATL-1–CHK-1 (ataxia telangiectasia mutated and Rad3 related–Chk1) checkpoint controls the timing of cell division in the future germ line, or P lineage, of the animal. Activation of the CHK-1 pathway by its canonical stimulus DNA damage is actively suppressed in early embryos so that P lineage cell divisions may occur on schedule. We recently found that the rad-2 mutation alleviates this checkpoint silent DNA damage response and, by doing so, causes damage-dependent delays in early embryonic cell cycle progression and subsequent lethality. In this study, we report that mutations in the smk-1 gene cause the rad-2 phenotype. SMK-1 is a regulatory subunit of the PPH-4.1 (protein phosphatase 4) protein phosphatase, and we show that SMK-1 recruits PPH-4.1 to replicating chromatin, where it silences the CHK-1 response to DNA damage. These results identify the SMK-1–PPH-4.1 complex as a critical regulator of the CHK-1 pathway in a developmentally relevant context.


2006 ◽  
Vol 17 (1) ◽  
pp. 336-344 ◽  
Author(s):  
Jayne M. Squirrell ◽  
Zachary T. Eggers ◽  
Nancy Luedke ◽  
Bonnie Saari ◽  
Andrew Grimson ◽  
...  

The division of one cell into two requires the coordination of multiple components. We describe a gene, car-1, whose product may provide a link between disparate cellular processes. Inhibition of car-1 expression in Caenorhabditis elegans embryos causes late cytokinesis failures: cleavage furrows ingress but subsequently regress and the spindle midzone fails to form, even though midzone components are present. The localized accumulation of membrane that normally develops at the apex of the cleavage furrow during the final phase of cytokinesis does not occur and organization of the endoplasmic reticulum is aberrant, indicative of a disruption in membrane trafficking. The car-1 gene has homologues in a number of species, including proteins that associate with RNA binding proteins. CAR-1 localizes to P-granules (germ-line specific ribonucleoprotein particles) and discrete, developmentally regulated cytoplasmic foci. These foci also contain DCAP-1, a protein involved in decapping mRNAs. Thus, CAR-1, a protein likely to be associated with RNA metabolism, plays an essential role in the late stage of cytokinesis, suggesting a novel link between RNA, membrane trafficking and cytokinesis in the C. elegans embryo.


Development ◽  
1997 ◽  
Vol 124 (11) ◽  
pp. 2191-2201 ◽  
Author(s):  
G. Seydoux ◽  
M.A. Dunn

Early embryonic germ cells in C. elegans and D. melanogaster fail to express many messenger RNAs expressed in somatic cells. In contrast, we find that ribosomal RNAs are expressed in both cell types. We show that this deficiency in mRNA production correlates with the absence of a specific phosphoepitope on the carboxy-terminal domain of RNA polymerase II. In both C. elegans and Drosophila embryos, this phosphoepitope appears in somatic nuclei coincident with the onset of embryonic transcription, but remains absent from germ cells until these cells associate with the gut primordium during gastrulation. In contrast, a second distinct RNA polymerase II phosphoepitope is present continuously in both somatic and germ cells. The germ-line-specific factor PIE-1 is required to block mRNA production in the germ lineage of early C. elegans embryos (Seydoux, G., Mello, C. C., Pettitt, J., Wood, W. B., Priess, J. R. and Fire, A. (1996) Nature 382, 713–716). We show here that PIE-1 is also required for the germ-line-specific pattern of RNA polymerase II phosphorylation. These observations link inhibition of mRNA production in embryonic germ cells to a specific modification in the phosphorylation pattern of RNA polymerase II and suggest that repression of RNA polymerase II activity may be part of an evolutionarily conserved mechanism that distinguishes germ line from soma during early embryogenesis. In addition, these studies also suggest that different phosphorylated isoforms of RNA polymerase II perform distinct functions.


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