Spermatogenesis is a complex differentiation process that involves the successive and simultaneous execution of three different gene expression programs: mitotic proliferation of spermatogonia, meiosis, and spermiogenesis. Testicular cell heterogeneity has hindered its molecular analyses. Moreover, the characterization of short, poorly represented cell stages such as initial meiotic prophase ones (leptotene and zygotene) has remained elusive, despite their crucial importance for understanding the fundamentals of meiosis.We have developed a flow cytometry-based approach for obtaining highly pure stage-specific spermatogenic cell populations, including early meiotic prophase. Here we combined this methodology with next generation sequencing, which enabled the analysis of meiotic and postmeiotic gene expression signatures in mouse with unprecedented reliability. Interestingly, we found that a considerable number of genes involved in early as well as late meiotic processes are already on at early meiotic prophase, with a high proportion of them being expressed only for the short time lapse of lepto-zygotene stages. Besides, we observed a massive change in gene expressionpatterns during medium meiotic prophase (pachytene) when mostly genes related to spermiogenesis and sperm function are already turned on. This indicates that the transcriptional switch from meiosis to post-meiosis takes place very early, during meiotic prophase, thus disclosing a higher incidence of post-transcriptional regulationin spermatogenesis than previously reported. Moreover, we found that a good proportion of the differential gene expression in spermiogenesis corresponds to up-regulation of genes whose expression starts earlier, at pachytene stage; this includes transition protein- and protamine-coding genes, which have long been claimed to switch on during spermiogenesis. In addition, our results afford new insights concerning X chromosome meiotic inactivation and reactivation. This work provides for the first time an overview of the time course for the massive onset and turning off of the meiotic and spermiogenic genetic programs. Importantly, our data represent a highly reliable information set about gene expression in pure testicular cell populations including early meiotic prophase, for further data mining towards the elucidation of the molecular bases of male reproduction in mammals.
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Sex, Specimen part, Cell line
View SamplesA genome-wide map of circular RNA in adult zebrafish.
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View SamplesThe origin of humans was accompanied by the emergence of new behavioral and cognitive functions, including language and specialized forms of abstract representation. However, the molecular foundations of these human capabilities are poorly understood. Because of the extensive similarity between human and chimpanzee DNA sequences, it has been suggested that many of the key phenotypic differences between species result primarily from alterations in the regulation of genes rather than in their sequences.
Elevated gene expression levels distinguish human from non-human primate brains.
Sex, Age, Specimen part
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AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.
Cell line
View SamplesEstrogen receptor (ER) is key player in the progression of breast cancer. ER binds to DNA and mediates long-range chromatin interactions throughout the genome, but the underlying mechanism in this process is unclear. Here, we show that AP-2 motifs are highly enriched in the ER binding sites (ERBS) identified from the recent ChIA-PET of ER. More importantly, we demonstrate that AP-2 (also known as TFAP2C), a member of the AP-2 family which has been implicated in breast cancer oncogenesis, is recruited to chromatin in a ligand-independent manner and co-localized with ER binding events. Furthermore, pertubation of AP-2 expression disrupts ER DNA binding, long-range chromatin interactions, and gene transcription. Using ChIP-seq, we show that AP-2 and ER binding occurs in close proximity on a genome-wide scale. The majority of these shared genomic regions are also occupied by the pioneer factor, FoxA1. AP-2 is required for efficient FoxA1 binding and vice versa. Finally, we show that most ERBS associated with long-range chromatin interactions are co-localized with both AP-2 and FoxA1. Together, our results suggest AP-2 is an essential factor in ER-mediated transcription, primarily working together with FoxA1 to facilitate ER binding and long-range chromatin interactions.
AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.
Cell line
View SamplesThe Mechanisms of Maize Resistance to Fusarium verticillioides by comprehensive analysis of RNA-seq Data
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Age, Specimen part, Disease, Disease stage, Treatment
View SamplesGene expression changes in mouse skeletal muscle were assessed in wild-type and Jhdm2a null skeletal muscle in an effort to define the role of Jhdm2a in energy expenditure and metabolism.
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance.
Sex, Age, Specimen part
View SamplesPolycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved at least partly through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Although recent studies have revealed the genome wide binding patterns of some of the PRC1 and PRC2 components, as well as the H3K27me3 mark, there have been no reports describing genome wide localization of uH2A. Using the recently developed ChIP-Seq technology, here we report genome wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We provide evidence to suggest that DNA methylation is tightly linked to H2A ubiquitylation in high density CpG promoters. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells.
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Sex
View SamplesRNA-Seq uncovers transcriptomic variations associated with the lethal phenotype conversion on LNCaP progression cell model
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
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Specimen part
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