Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA387083 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:An erythroid-specific enhancer of ATP2B4 mediates red blood cell hydration and malaria susceptibility
| PRJNA386912 | ENA
Project description:An erythroid-specific enhancer of ATP2B4 mediates red blood cell hydration and malaria susceptibility [RNA-seq]
| PRJNA356268 | ENA
Project description:Few genotype-phenotype associations identified by genome-wide association studies (GWAS) have been defined mechanistically, precluding thorough assessment of their impact on human health. We conducted an expression quantitative trait loci (eQTL) mapping analysis in human erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (RBC). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4-/- mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine-mapped the genetic signal to an erythroid-specific enhancer bound by GATA1 and TAL1. These results illustrate the importance to combine transcriptome, epigenome, and genome editing approaches in phenotype-relevant cells to characterize non-coding regulatory elements associated with human complex diseases and traits. Our studies suggest ATP2B4 as a potential target to modulate RBC hydration in erythroid disorders and malaria infection.
2017-07-17 | GSE98992 | GEO
Project description:Few genotype-phenotype associations identified by genome-wide association studies (GWAS) have been defined mechanistically, precluding thorough assessment of their impact on human health. We conducted an expression quantitative trait loci (eQTL) mapping analysis in human erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (RBC). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4-/- mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine-mapped the genetic signal to an erythroid-specific enhancer bound by GATA1 and TAL1. These results illustrate the importance to combine transcriptome, epigenome, and genome editing approaches in phenotype-relevant cells to characterize non-coding regulatory elements associated with human complex diseases and traits. Our studies suggest ATP2B4 as a potential target to modulate RBC hydration in erythroid disorders and malaria infection.
2017-06-23 | GSE90878 | GEO
Project description:We analyzed the transcriptional effects of transgenic expression of our erythroid-specific codon-optimized GATA1 lentiviral vector in differentiating red blood cells of patients diagnosed with Diamond-Blackfan anemia.
2024-10-14 | GSE261450 | GEO
Project description:Posttranscriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process can have detrimental effects on normal development and give rise to various diseases. The search for novel posttranscriptional regulators and the exploration of their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait GWASs and transcriptomes of erythropoiesis, we identified FAM46C, a non-canonical RNA poly(A) polymerase, as a necessary factor for proper red blood cell development. FAM46C is highly expressed in late stages of the erythroid lineage, and its developmental upregulation is controlled by an erythroid-specific enhancer. We demonstrate that FAM46C stabilizes mRNA in an enzyme activity dependent manner by maintaining the poly(A) tails of its targets. Furthermore, we identified transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C, which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis. In conclusion, our study unveils a novel role of FAM46C in positively regulating the level of lysosome and mitochondria components, thereby promoting erythropoiesis.
2023-10-20 | GSE245696 | GEO
Project description:Posttranscriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process can have detrimental effects on normal development and give rise to various diseases. The search for novel posttranscriptional regulators and the exploration of their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait GWASs and transcriptomes of erythropoiesis, we identified FAM46C, a non-canonical RNA poly(A) polymerase, as a necessary factor for proper red blood cell development. FAM46C is highly expressed in late stages of the erythroid lineage, and its developmental upregulation is controlled by an erythroid-specific enhancer. We demonstrate that FAM46C stabilizes mRNA in an enzyme activity dependent manner by maintaining the poly(A) tails of its targets. Furthermore, we identified transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C, which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis. In conclusion, our study unveils a novel role of FAM46C in positively regulating the level of lysosome and mitochondria components, thereby promoting erythropoiesis.
2023-10-20 | GSE245695 | GEO
Project description:Posttranscriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process can have detrimental effects on normal development and give rise to various diseases. The search for novel posttranscriptional regulators and the exploration of their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait GWASs and transcriptomes of erythropoiesis, we identified FAM46C, a non-canonical RNA poly(A) polymerase, as a necessary factor for proper red blood cell development. FAM46C is highly expressed in late stages of the erythroid lineage, and its developmental upregulation is controlled by an erythroid-specific enhancer. We demonstrate that FAM46C stabilizes mRNA in an enzyme activity dependent manner by maintaining the poly(A) tails of its targets. Furthermore, we identified transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C, which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis. In conclusion, our study unveils a novel role of FAM46C in positively regulating the level of lysosome and mitochondria components, thereby promoting erythropoiesis.
2023-10-20 | GSE245694 | GEO
Project description:Posttranscriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process can have detrimental effects on normal development and give rise to various diseases. The search for novel posttranscriptional regulators and the exploration of their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait GWASs and transcriptomes of erythropoiesis, we identified FAM46C, a non-canonical RNA poly(A) polymerase, as a necessary factor for proper red blood cell development. FAM46C is highly expressed in late stages of the erythroid lineage, and its developmental upregulation is controlled by an erythroid-specific enhancer. We demonstrate that FAM46C stabilizes mRNA in an enzyme activity dependent manner by maintaining the poly(A) tails of its targets. Furthermore, we identified transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C, which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis. In conclusion, our study unveils a novel role of FAM46C in positively regulating the level of lysosome and mitochondria components, thereby promoting erythropoiesis.
2023-10-20 | GSE245693 | GEO
Project description:Posttranscriptional regulation of mRNA is a crucial component of gene expression. The disruption of this process can have detrimental effects on normal development and give rise to various diseases. The search for novel posttranscriptional regulators and the exploration of their roles are essential for understanding development and disease. Through a multimodal analysis of red blood cell trait GWASs and transcriptomes of erythropoiesis, we identified FAM46C, a non-canonical RNA poly(A) polymerase, as a necessary factor for proper red blood cell development. FAM46C is highly expressed in late stages of the erythroid lineage, and its developmental upregulation is controlled by an erythroid-specific enhancer. We demonstrate that FAM46C stabilizes mRNA in an enzyme activity dependent manner by maintaining the poly(A) tails of its targets. Furthermore, we identified transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C, which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis. In conclusion, our study unveils a novel role of FAM46C in positively regulating the level of lysosome and mitochondria components, thereby promoting erythropoiesis.
2023-10-20 | GSE245692 | GEO