scholarly journals DAZL is a master translational regulator of murine spermatogenesis

2018 ◽  
Author(s):  
Haixin Li ◽  
Zhuqing Liang ◽  
Jian Yang ◽  
Dan Wang ◽  
Hanben Wang ◽  
...  
Keyword(s):  
Germ Cells ◽  
Drastic Reduction ◽  
Developmental Arrest ◽  
Genome Wide ◽  
Gradual Loss ◽  
Mrna Transcripts ◽  
Development And Differentiation ◽  
Postnatal Stage ◽  
Specific Deletion

Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells and essential for embryonic germ cell development and differentiation, yet gametogenic function of DAZL has not been fully characterized with most of its in vivo direct targets unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells (SSCs), meiotic arrest and spermatid arrest respectively. Using the genome-wide HITS-CLIP and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at 3′ UnTranslated Region (3′ UTR) and interacted with translation proteins including PABP. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts were significantly decreased, resulting in drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.

scholarly journals DAZL is a master translational regulator of murine spermatogenesis

2018 ◽  
Vol 6 (3) ◽  
pp. 455-468 ◽  
Author(s):  
Haixin Li ◽  
Zhuqing Liang ◽  
Jian Yang ◽  
Dan Wang ◽  
Hanben Wang ◽  
...  
Keyword(s):  
Germ Cells ◽  
High Throughput Sequencing ◽  
Drastic Reduction ◽  
Developmental Arrest ◽  
Genome Wide ◽  
Gradual Loss ◽  
Development And Differentiation ◽  
Postnatal Stage ◽  
Specific Deletion

Abstract Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells, and is essential for embryonic germ cell development and differentiation, yet the gametogenic function of DAZL has not been fully characterized and most of its in vivo direct targets remain unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells, meiotic arrest and spermatid arrest. Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at the 3′-untranslated region and interacted with translation proteins including poly(A) binding protein. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts, were significantly decreased, resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.

scholarly journals DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease

2017 ◽  
Vol 114 (36) ◽  
pp. E7526-E7535 ◽  
Author(s):  
Danuta M. Jeziorska ◽  
Robert J. S. Murray ◽  
Marco De Gobbi ◽  
Ricarda Gaentzsch ◽  
David Garrick ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Cpg Islands ◽  
Naturally Occurring ◽  
Genome Wide ◽  
A Genome ◽  
Primary Determinant ◽  
Development And Differentiation ◽  
Intrinsic Capacity

The human genome contains ∼30,000 CpG islands (CGIs). While CGIs associated with promoters nearly always remain unmethylated, many of the ∼9,000 CGIs lying within gene bodies become methylated during development and differentiation. Both promoter and intragenic CGIs may also become abnormally methylated as a result of genome rearrangements and in malignancy. The epigenetic mechanisms by which some CGIs become methylated but others, in the same cell, remain unmethylated in these situations are poorly understood. Analyzing specific loci and using a genome-wide analysis, we show that transcription running across CGIs, associated with specific chromatin modifications, is required for DNA methyltransferase 3B (DNMT3B)-mediated DNA methylation of many naturally occurring intragenic CGIs. Importantly, we also show that a subgroup of intragenic CGIs is not sensitive to this process of transcription-mediated methylation and that this correlates with their individual intrinsic capacity to initiate transcription in vivo. We propose a general model of how transcription could act as a primary determinant of the patterns of CGI methylation in normal development and differentiation, and in human disease.

Thymus involution induced by 5-azacytidine

1986 ◽  
Vol 6 (7) ◽  
pp. 603-612 ◽  
Author(s):  
Adam Csordas ◽  
Konrad Schauenstein
Keyword(s):  
Concanavalin A ◽  
Marked Reduction ◽  
Spleen Weight ◽  
Drastic Reduction ◽  
Thymus Involution ◽  
Development And Differentiation ◽  
Per Se ◽  
Cell Mitogen ◽  
In Vivo Effects

Hypomethylation of DNA, which can be achieved by incorporation of 5-azacytidine, has been correlated with derepression of genes. In order to examine the in vivo effects of 5-azacytidine on organ development and differentiation, young rats were treated with the drug. There was an almost complete reduction of thymus and a marked reduction of spleen weight, while other organs, including testes were only marginally affected. Control experiments with cytosine-arabinoside suggest that treatment with an inhibitor of DNA replication per se is not responsible for the very rapid thymus involution triggered by 5-azacytidine in rats. In spite of the drastic reduction of thymus and spleen weight, lymphocytes of these organs were not impaired in their response to the T cell mitogen Concanavalin A.

Formation of a large Vasa-positive germ granule and its inheritance by germ cells in the enigmatic Chaetognaths

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 661-670 ◽  
Author(s):  
Danièle Carré ◽  
Chakib Djediat ◽  
Christian Sardet
Keyword(s):  
Germ Cells ◽  
Molecular Mechanisms ◽  
Germ Plasm ◽  
Germ Line ◽  
Germinal Vesicle ◽  
Phylogenetic Position ◽  
Internal Fertilization ◽  
Cell Stage ◽  
Development And Differentiation

Chaetognaths (arrow worms) are abundant hermaphrodite marine organisms whose phylogenetic position amongst protostomes and deuterostomes is still debated. Ancient histological observations dating from a century ago described the presence in eggs of a large granule, presumed to be a germ plasm, and its probable inheritance in four primary germ cells (PGCs). Using videomicroscopy, electron microscopy and immunocytochemistry (labelling with anti-Vasa antibodies) we have followed the cycle of aggregation and dispersion of germ plasm and nuage material in eggs, embryos, PGCs and oocytes in several species of benthic (Spadella) and planctonic (Sagitta) chaetognaths. In these animals, germ cells and gametes can be observed in vivo throughout the 1-2 month life cycle.After describing internal fertilization in live animals we show that the single large (15 μm diameter) germ granule forms by a spiralling aggregation movement of small germ islands situated in the vegetal cortex at the time of first mitosis. We also demonstrate that the granule forms autonomously in unfertilized activated eggs or fertilized egg fragments. Once formed, the germ granule first associates with the cleavage furrow and is segregated into one of the first two blastomeres. The germ granule is then translocated from the cortex to the mitotic spindle during 3rd cleavage and remains in the single most-vegetal blastomere until the 32-cell stage. At the 64-cell stage the germ granule is partitioned as nuage material into two founder PGCs and further partitioned into four PGCs situated at the tip of the archenteron during gastrulation. These four PGCs migrate without dividing to reach the transverse septum, then proliferate and differentiate into oocytes and spermatocytes of two ovaries and two testes. We noted that germ plasm and nuage material were associated with mitochondria, the nucleus, the spindle and the centrosome during some stages of development and differentiation of the germ line. Finally, we demonstrate that a Vasa-like protein is present in the germ granule, in PGCs and in the electron-dense material associated with the germinal vesicle of oocytes. These features stress the conservation of cellular and molecular mechanisms involved in germ cell determination.Movies available on-line

scholarly journals Epigenetic initiation of the TH17 differentiation program is promoted by Cxxc finger protein 1

2019 ◽  
Vol 5 (10) ◽  
pp. eaax1608 ◽  
Author(s):  
Feng Lin ◽  
Xiaoyu Meng ◽  
Yixin Guo ◽  
Wenqiang Cao ◽  
Wanlu Liu ◽  
...  
Keyword(s):  
Autoimmune Encephalomyelitis ◽  
Stat3 Signaling ◽  
Finger Protein ◽  
Genome Wide ◽  
Th17 Differentiation ◽  
Specific Deletion ◽  
Experimental Autoimmune ◽  
Cxxc Finger Protein 1

IL-6/STAT3 signaling is known to initiate the TH17 differentiation program, but the upstream regulatory mechanisms remain minimally explored. Here, we show that Cxxc finger protein 1 (Cxxc1) promoted the generation of TH17 cells as an epigenetic regulator and prevented their differentiation into Treg cells. Mice with a T cell–specific deletion of Cxxc1 were protected from experimental autoimmune encephalomyelitis and were more susceptible to Citrobacter rodentium infection. Cxxc1 deficiency decreased IL-6Rα expression and impeded IL-6/STAT3 signaling, whereas the overexpression of IL-6Rα could partially reverse the defects in Cxxc1-deficient TH17 cells in vitro and in vivo. Genome-wide occupancy analysis revealed that Cxxc1 bound to Il6rα gene loci by maintaining the appropriate H3K4me3 modification of its promoter. Therefore, these data highlight that Cxxc1 as a key regulator governs the balance between TH17 and Treg cells by controlling the expression of IL-6Rα, which affects IL-6/STAT3 signaling and has an impact on TH17-related autoimmune diseases.

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