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A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site
- Source :
- Blood 120 (2012): 4859–4868. doi:10.1182/blood-2012-01-401893, info:cnr-pdr/source/autori:Nurnberg ST, Rendon A, Smethurst PA, Paul DS, Voss K, Thon JN, Lloyd-Jones H, Sambrook JG, Tijssen MR; HaemGen Consortium, Italiano JE Jr, Deloukas P, Gottgens B, Soranzo N, Ouwehand WH./titolo:A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site./doi:10.1182%2Fblood-2012-01-401893/rivista:Blood/anno:2012/pagina_da:4859/pagina_a:4868/intervallo_pagine:4859–4868/volume:120, Nürnberg, S T, Rendon, A, Smethurst, P A, Paul, D S, Voss, K, Thon, J N, Lloyd-Jones, H, Sambrook, J G, Tijssen, M R, Hottenga, J J, de Geus, E J C, Willemsen, G, Boomsma, D I, Italiano Jr, J E, Deloukas, P, Gottgens, B, Soranzo, N & Ouwehand, W H 2012, ' A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site ', Blood, vol. 120, no. 24, pp. 4859-4868 . https://doi.org/10.1182/blood-2012-01-401893, Blood, 120(24), 4859-4868. American Society of Hematology, Nürnberg, S T, Rendon, A, Smethurst, P A, Paul, D S, Voss, K, Thon, J N, Lloyd-Jones, H, Sambrook, J G, Tijssen, M R, Italiano, J E, Deloukas, P, Gottgens, B, Soranzo, N, Ouwehand, W H & Pirastu, N 2012, ' A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site ', Blood, vol. 120, no. 24, pp. 4859-68 . https://doi.org/10.1182/blood-2012-01-401893
- Publication Year :
- 2013
-
Abstract
- We recently identified 68 genomic loci where common sequence variants are associated with platelet count and volume. Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly controlled by transcription factors. The homeobox transcription factor MEIS1 is uniquely transcribed in megakaryocytes and not in the other lineage-committed blood cells. By ChIP-seq, we show that 5 of the 68 loci pinpoint a MEIS1 binding event within a group of 252 MK-overexpressed genes. In one such locus in DNM3, regulating platelet volume, the MEIS1 binding site falls within a region acting as an alternative promoter that is solely used in megakaryocytes, where allelic variation dictates different levels of a shorter transcript. The importance of dynamin activity to the latter stages of thrombopoiesis was confirmed by the observation that the inhibitor Dynasore reduced murine proplatelet for-mation in vitro.
- Subjects :
- Netherlands Twin Register (NTR)
Transcription, Genetic
Gene Expression
Biochemistry
megakaryocyte
Mice
DNM3 promoter
Transcription (biology)
GWAS
Platelet
Thrombopoiesis
Myeloid Ecotropic Viral Integration Site 1 Protein
Promoter Regions, Genetic
Cells, Cultured
Reverse Transcriptase Polymerase Chain Reaction
Hematology
Neoplasm Proteins
Haematopoiesis
Transcription Initiation Site
Megakaryocytes
platelet volume
DNM3
megakaryocytes
MEIS1
Blood Platelets
Chromatin Immunoprecipitation
Immunology
Biology
Polymorphism, Single Nucleotide
MEIS1 binding site
SDG 3 - Good Health and Well-being
Cell Line, Tumor
Animals
Humans
Cell Lineage
Binding site
Gene
Transcription factor
Homeodomain Proteins
Binding Sites
Genome, Human
Platelet Count
Hydrazones
Genetic Variation
Cell Biology
Sequence Analysis, DNA
Platelets and Thrombopoiesis
Molecular biology
Dynamin III
Subjects
Details
- Language :
- English
- ISSN :
- 00064971
- Database :
- OpenAIRE
- Journal :
- Blood 120 (2012): 4859–4868. doi:10.1182/blood-2012-01-401893, info:cnr-pdr/source/autori:Nurnberg ST, Rendon A, Smethurst PA, Paul DS, Voss K, Thon JN, Lloyd-Jones H, Sambrook JG, Tijssen MR; HaemGen Consortium, Italiano JE Jr, Deloukas P, Gottgens B, Soranzo N, Ouwehand WH./titolo:A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site./doi:10.1182%2Fblood-2012-01-401893/rivista:Blood/anno:2012/pagina_da:4859/pagina_a:4868/intervallo_pagine:4859–4868/volume:120, Nürnberg, S T, Rendon, A, Smethurst, P A, Paul, D S, Voss, K, Thon, J N, Lloyd-Jones, H, Sambrook, J G, Tijssen, M R, Hottenga, J J, de Geus, E J C, Willemsen, G, Boomsma, D I, Italiano Jr, J E, Deloukas, P, Gottgens, B, Soranzo, N & Ouwehand, W H 2012, ' A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site ', Blood, vol. 120, no. 24, pp. 4859-4868 . https://doi.org/10.1182/blood-2012-01-401893, Blood, 120(24), 4859-4868. American Society of Hematology, Nürnberg, S T, Rendon, A, Smethurst, P A, Paul, D S, Voss, K, Thon, J N, Lloyd-Jones, H, Sambrook, J G, Tijssen, M R, Italiano, J E, Deloukas, P, Gottgens, B, Soranzo, N, Ouwehand, W H & Pirastu, N 2012, ' A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site ', Blood, vol. 120, no. 24, pp. 4859-68 . https://doi.org/10.1182/blood-2012-01-401893
- Accession number :
- edsair.doi.dedup.....ae2e64f26a5f52ff78d19ed098857b3b