We are analyzing https://link.springer.com/article/10.1186/s13073-014-0122-2.

Title:
Comparison of DNA methylation profiles in human fetal and adult red blood cell progenitors | Genome Medicine
Description:
Background DNA methylation is an epigenetic modification that plays an important role during mammalian development. Around birth in humans, the main site of red blood cell production moves from the fetal liver to the bone marrow. DNA methylation changes at the β-globin locus and a switch from fetal to adult hemoglobin production characterize this transition. Understanding this globin switch may improve the treatment of patients with sickle cell disease and β-thalassemia, two of the most common Mendelian diseases in the world. The goal of our study was to describe and compare the genome-wide patterns of DNA methylation in fetal and adult human erythroblasts. Methods We used the Illumina HumanMethylation 450 k BeadChip to measure DNA methylation at 402,819 CpGs in ex vivo-differentiated erythroblasts from 12 fetal liver and 12 bone marrow CD34+ donors. Results We identified 5,937 differentially methylated CpGs that overlap with erythroid enhancers and binding sites for erythropoiesis-related transcription factors. Combining this information with genome-wide association study results, we show that erythroid enhancers define particularly promising genomic regions to identify new genetic variants associated with fetal hemoglobin (HbF) levels in humans. Many differentially methylated CpGs are located near genes with unanticipated roles in red blood cell differentiation and proliferation. For some of these new candidate genes, we confirm the correlation between DNA methylation and gene expression levels in red blood cell progenitors. We also provide evidence that DNA methylation and genetic variation at the β-globin locus independently control globin gene expression in adult erythroblasts. Conclusions Our DNA methylome maps confirm the widespread dynamic changes in DNA methylation that occur during human erythropoiesis. These changes tend to happen near erythroid enhancers, further highlighting their importance in erythroid regulation and HbF production. Finally, DNA methylation may act independently of the transcription factor BCL11A to repress fetal hemoglobin production. This provides cues on strategies to more efficiently re-activate HbF production in sickle cell disease and β-thalassemia patients.
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Keywords {🔍}

dna, methylation, erythroblasts, fetal, pubmed, cpgs, article, adult, cell, gene, expression, google, scholar, erythroid, enhancers, methylated, cas, differentially, cells, hbf, figure, human, central, additional, genes, transcription, levels, enrichment, file, analysis, production, hemoglobin, promoter, table, data, binding, erythropoiesis, bcla, blood, illumina, results, differentiation, bone, factor, promoters, hypomethylated, hbg, liver, βglobin, genome,

Topics {✒️}

profile dna methylation article download pdf investigators monitored genome-wide maldi-tof mass spectrometry measure genome-wide patterns species-divergent globin switching main stage-specific clusters article lessard dna methylation profiles erythropoiesis-related transcription factors phase serum-free culture treat β-hemoglobinopathy patients g-csf receptor expression beta-globin gene locus paired-end rna sequencing beta-globin gene switching hbg2/hbb expression ratio illumina human610-quad array dna methylation β-values bone marrow-derived erythroblasts distal regulatory elements genome-wide patterns comparing methylation β-values demethylating 5-aza-2’-deoxycytidine full size image adult erythroblast bonferonni-adjusted statistical threshold population-based linkage analyses stage-specific erythroid enhancers performed quality-control steps roadmap epigenomics project transcription factor bcl11a kindly providing access transcription factor important author information authors cold spring harbor view guillaume lettre hematopoietic stem cell murine hematopoietic stem search gata binding motifs sankaran vg top transcription factors twins reveals links controls beta-globin comprehensive functional analysis cell stem cell β-globin locus privacy choices/manage cookies

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WebPage:
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         headline:Comparison of DNA methylation profiles in human fetal and adult red blood cell progenitors
         description:DNA methylation is an epigenetic modification that plays an important role during mammalian development. Around birth in humans, the main site of red blood cell production moves from the fetal liver to the bone marrow. DNA methylation changes at the β-globin locus and a switch from fetal to adult hemoglobin production characterize this transition. Understanding this globin switch may improve the treatment of patients with sickle cell disease and β-thalassemia, two of the most common Mendelian diseases in the world. The goal of our study was to describe and compare the genome-wide patterns of DNA methylation in fetal and adult human erythroblasts. We used the Illumina HumanMethylation 450 k BeadChip to measure DNA methylation at 402,819 CpGs in ex vivo-differentiated erythroblasts from 12 fetal liver and 12 bone marrow CD34+ donors. We identified 5,937 differentially methylated CpGs that overlap with erythroid enhancers and binding sites for erythropoiesis-related transcription factors. Combining this information with genome-wide association study results, we show that erythroid enhancers define particularly promising genomic regions to identify new genetic variants associated with fetal hemoglobin (HbF) levels in humans. Many differentially methylated CpGs are located near genes with unanticipated roles in red blood cell differentiation and proliferation. For some of these new candidate genes, we confirm the correlation between DNA methylation and gene expression levels in red blood cell progenitors. We also provide evidence that DNA methylation and genetic variation at the β-globin locus independently control globin gene expression in adult erythroblasts. Our DNA methylome maps confirm the widespread dynamic changes in DNA methylation that occur during human erythropoiesis. These changes tend to happen near erythroid enhancers, further highlighting their importance in erythroid regulation and HbF production. Finally, DNA methylation may act independently of the transcription factor BCL11A to repress fetal hemoglobin production. This provides cues on strategies to more efficiently re-activate HbF production in sickle cell disease and β-thalassemia patients.
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      headline:Comparison of DNA methylation profiles in human fetal and adult red blood cell progenitors
      description:DNA methylation is an epigenetic modification that plays an important role during mammalian development. Around birth in humans, the main site of red blood cell production moves from the fetal liver to the bone marrow. DNA methylation changes at the β-globin locus and a switch from fetal to adult hemoglobin production characterize this transition. Understanding this globin switch may improve the treatment of patients with sickle cell disease and β-thalassemia, two of the most common Mendelian diseases in the world. The goal of our study was to describe and compare the genome-wide patterns of DNA methylation in fetal and adult human erythroblasts. We used the Illumina HumanMethylation 450 k BeadChip to measure DNA methylation at 402,819 CpGs in ex vivo-differentiated erythroblasts from 12 fetal liver and 12 bone marrow CD34+ donors. We identified 5,937 differentially methylated CpGs that overlap with erythroid enhancers and binding sites for erythropoiesis-related transcription factors. Combining this information with genome-wide association study results, we show that erythroid enhancers define particularly promising genomic regions to identify new genetic variants associated with fetal hemoglobin (HbF) levels in humans. Many differentially methylated CpGs are located near genes with unanticipated roles in red blood cell differentiation and proliferation. For some of these new candidate genes, we confirm the correlation between DNA methylation and gene expression levels in red blood cell progenitors. We also provide evidence that DNA methylation and genetic variation at the β-globin locus independently control globin gene expression in adult erythroblasts. Our DNA methylome maps confirm the widespread dynamic changes in DNA methylation that occur during human erythropoiesis. These changes tend to happen near erythroid enhancers, further highlighting their importance in erythroid regulation and HbF production. Finally, DNA methylation may act independently of the transcription factor BCL11A to repress fetal hemoglobin production. This provides cues on strategies to more efficiently re-activate HbF production in sickle cell disease and β-thalassemia patients.
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         Transcription Factor Binding Motif
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         Adult Erythroid Cell
         Human Genetics
         Metabolomics
         Bioinformatics
         Medicine/Public Health
         general
         Cancer Research
         Systems Biology
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      affiliation:
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               type:PostalAddress
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