In the urinary tract, smooth muscle (SM) is present in the renal pelvis, the ureter, the bladder and the urethra and plays a crucial role in the functional and structural integrity of these organs. In Tshz3 mutant ureters the myogenic program is not activated in the proximal region due to the absence of expression of myocardin (Myocd), a key regulator of SM differentiation. We set out to characterize TSHZ3-dependent mechanisms that participate to the process of ureteric smooth muscle cells (SMC) differentiation.
The tiptop/teashirt genes regulate cell differentiation and renal physiology in Drosophila.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin.
Cell line, Treatment, Time
View SamplesMultiple signaling pathways ultimately modulate the epigenetic information embedded in the chromatin of gene promoters by recruiting epigenetic enzymes. We found that, in estrogen-regulated gene programming, the acetyltransferase CREB-binding protein (CBP) is specifically and exclusively methylated by the coactivator-associated arginine methyltransferase (CARM1) in vivo. CARM1-dependent CBP methylation and p160 coactivators were required for estrogen-induced recruitment to chromatin targets. Notably, methylation increased the histone acetyltransferase (HAT) activity of CBP and stimulated its autoacetylation. Comparative genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) studies revealed a variety of patterns by which p160, CBP, and methyl-CBP (meCBP) are recruited (or not) by estrogen to chromatin targets. Moreover, significant target gene-specific variation in the recruitment of (1) the p160 RAC3 protein, (2) the fraction of a given meCBP species within the total CBP, and (3) the relative recruitment of different meCBP species suggests the existence of a target gene-specific fingerprint for coregulator recruitment. Crossing ChIP-seq and transcriptomics profiles revealed the existence of meCBP hubs within the network of estrogen-regulated genes. Together, our data provide evidence for an unprecedented mechanism by which CARM1-dependent CBP methylation results in gene-selective association of estrogen-recruited meCBP species with different HAT activities and specifies distinct target gene hubs, thus diversifying estrogen receptor programming.
Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin.
Cell line, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
Sex, Age
View SamplesEpigenetic information can be inherited through the mammalian germline, and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information occurs in mammals, we carried out an expression profiling screen for genes in mice that responded to paternal diet.
Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
No sample metadata fields
View SamplesParental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: IVF was carried out using oocytes from females fed Control diet (C) and sperm from males fed Control diet or Low Protein diet (LP). Zygotes were then developed 2 cell (2C), 4 cell (4C), 8 cell (8C), Morula (M) or Blastocyst (B) embryonic developmental stages when single embryo RNA seq was carried out to study gene expression changes.
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Cell line, Subject
View SamplesParental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: Zygotes were generated by IVF from animals fed a control diet. These embryos were then microinjected with various combinations of small RNAs and control RNA (HIS3.3::GFP). Follwoing injections the zygotes were developed and allowed to develop until 2 cell (2C) or 4 cell (4C) stage when single embryo RNA seq was carried out to study gene expression changes
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Cell line, Subject
View SamplesParental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: Zygotes were generated by ICSI from oocytes/females fed a Control diet and sperm/males fed either a Control or Low Protein diet. The sperm was isolated from either the Rete testis or the Cauda epididymis and injected either as a whole sperm or just the sperm head. Following fertilization by ICSI the zygotes developed for 28 hours (2C stage) and were harvested for single-embryo RNA-Seq.
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Cell line, Subject
View SamplesThe cytokine IL-2 determines T cell fate by controlling T cell proliferation and differentiation, but the expression files of IL-2 regulated genes are not defined
Identification of expression patterns of IL-2-responsive genes in the murine T cell line CTLL-2.
No sample metadata fields
View SamplesStudy of single and double mutants of the two roX RNAs in D. melanogaster Overall design: Study of single and double mutants of the two roX RNAs in D. melanogaster
RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation.
Specimen part, Cell line, Subject
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