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Epigenetic dissecti...
Epigenetic dissection of human blood group genes reveals regulatory elements and detailed characteristics of KEL and four other loci
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- Wu, Ping Chun (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Transfusionsmedicin,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transfusion Medicine,Lund University Research Groups
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- McGowan, Eunike C. (författare)
- Lund University,Lunds universitet,Transfusionsmedicin,Forskargrupper vid Lunds universitet,Transfusion Medicine,Lund University Research Groups
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- Lee, Yan Quan (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Transfusionsmedicin,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transfusion Medicine,Lund University Research Groups
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- Ghosh, Sudip (författare)
- Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Proteomisk hematologi,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Proteomic Hematology,Lund University Research Groups
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- Hansson, Jenny (författare)
- Lund University,Lunds universitet,Proteomisk hematologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Proteomic Hematology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Olsson, Martin L. (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Transfusionsmedicin,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transfusion Medicine,Lund University Research Groups,Region Skåne
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(creator_code:org_t)
- 2024
- 2024
- Engelska 14 s.
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Ingår i: Transfusion. - 0041-1132. ; 64:6, s. 1083-1096
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Blood typing is essential for safe transfusions and is performed serologically or genetically. Genotyping predominantly focuses on coding regions, but non-coding variants may affect gene regulation, as demonstrated in the ABO, FY and XG systems. To uncover regulatory loci, we expanded a recently developed bioinformatics pipeline for discovery of non-coding variants by including additional epigenetic datasets. Methods: Multiple datasets including ChIP-seq with erythroid transcription factors (TFs), histone modifications (H3K27ac, H3K4me1), and chromatin accessibility (ATAC-seq) were analyzed. Candidate regulatory regions were investigated for activity (luciferase assays) and TF binding (electrophoretic mobility shift assay, EMSA, and mass spectrometry, MS). Results: In total, 814 potential regulatory sites in 47 blood-group-related genes were identified where one or more erythroid TFs bound. Enhancer candidates in CR1, EMP3, ABCB6, and ABCC4 indicated by ATAC-seq, histone markers, and co-occupancy of 4 TFs (GATA1/KLF1/RUNX1/NFE2) were investigated but only CR1 and ABCC4 showed increased transcription. Co-occupancy of GATA1 and KLF1 was observed in the KEL promoter, previously reported to contain GATA1 and Sp1 sites. TF binding energy scores decreased when three naturally occurring variants were introduced into GATA1 and KLF1 motifs. Two of three GATA1 sites and the KLF1 site were confirmed functionally. EMSA and MS demonstrated increased GATA1 and KLF1 binding to the wild-type compared to variant motifs. Discussion: This combined bioinformatics and experimental approach revealed multiple candidate regulatory regions and predicted TF co-occupancy sites. The KEL promoter was characterized in detail, indicating that two adjacent GATA1 and KLF1 motifs are most crucial for transcription.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- blood group
- enhancers
- epigenetics
- gene regulation
- KEL
- transcription factors
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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