Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci.

Details

Serval ID
serval:BIB_4373C8616789
Type
Article: article from journal or magazin.
Collection
Publications
Title
Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci.
Journal
Genome research
Author(s)
Paul D.S., Albers C.A., Rendon A., Voss K., Stephens J., van der Harst P., Chambers J.C., Soranzo N., Ouwehand W.H., Deloukas P.
Working group(s)
HaemGen Consortium
Contributor(s)
Akkerman J.W., Albers C.A., Algra A., Al-Hussani A., Allayee H., Anni F., Asselbergs F.W., Attwood A., Balkau B., Bandinelli S., Bastardot F., Basu S., Baumeister S.E., Beckmann J., Benyamin B., Biino G., Bis J.C., Bomba L., Bonnefond A., Boomsma D.I., Bradley J.R., Cambien F., Chambers J.C., Ciullo M., Cookson W.O., Cucca F., Cvejic A., D'Adamo A.P., Danesh J., Danjou F., Das D., Davies G., de Bakker P.I., de Boer R.A., de Geus E.J., Deary I.J., Dedoussis G.V., Deloukas P., Dimitriou M., Dina C., Döring A., Elling U., Ellinghaus D., Elliott P., Engström G., Erdmann J., Esko T., Evans D.M., Eyjolfsson G.I., Falchi M., Feng W., Ferreira M.A., Ferrucci L., Fischer K., Folsom A.R., Fortina P., Franke A., Franke L., Frazer I.H., Froguel P., Galanello R., Ganesh S.K., Garner S.F., Gasparini P., Genser B., Gibson Q.D., Gieger C., Girotto G., Glazer N.L., Gögele M., Goodall A.H., Greinacher A., Gudbjartsson D.F., Hammond C., Harris S.E., Hartiala J., Hartikainen A.L., Hazen S.L., Heckbert S.R., Hedblad B., Hengstenberg C., Hersch M., Hicks A.A., Holm H., Hottenga J.J., Illig T., Jarvelin M.R., Jolley J., Jupe S., Kähönen M., Kamatani N., Kanoni S., Kema I.P., Kemp J.P., Khadake J., Khaw K.T., Kleber M.E., Kooner J.S., Kovacs P., Kühnel B., Kyrtsonis M.C., Labrune Y., Lagou V., Langenberg C., Lehtimäki T., Li X., Liang L., Lloyd-Jones H., Loos R.J., Lopez L.M., Lumley T., Lyytikäinen L.P., Maerz W., Mägi R., Mangino M., Martin N.G., Maschio A., Mateo Leach I., McKnight B., Meacham S., Medland S.E., Meisinger C., Melander O., Memari Y., Metspalu A., Miller K., Mitchell B.D., Moffatt M.F., Montgomery G.W., Moore C., Murgia F., Nakamura Y., Nauck M., Navis G., Nolte I.M., Nöthlings U., Nutile T., Okada Y., Olafsson I., Onundarson P.T., O'Reilly P.F., Ouwehand W.H., Parracciani D., Parsa A., Paul D.S., Penninger J.M., Penninx B.W., Pirastu M., Pirastu N., Pistis G., Porcu E., Portas L., Porteous D., Pouta A., Pramstaller P.P., Prokopenko I., Psaty B.M., Pullat J., Radhakrishnan A., Raitakari O., Ramirez-Solis R., Rendon A., Ried J.S., Ring S.M., Robino A., Rotter J.I., Ruggiero D., Ruokonen A., Sala C., Saluments A., Samani N.J., Sambrook J., Sanna S., Schlessinger D., Schmidt C.O., Schreiber S., Schunkert H., Scott J., Sehmi J., Serbanovic-Canic J., Shin S.Y., Shuldiner A.R., Sladek R., Smit J.H., Smith G.D., Smith J.G., Smith N.L., Snieder H., Soranzo N., Sorice R., Spector T.D., Starr J.M., Stefansson K., Stemple D., Stephens J., Stumvoll M., Sulem P., Takahashi A., Tan S.T., Tanaka T., Tang C., Tang W., Tang W.H., Taylor K., Tenesa A., Teumer A., Thein S.L., Thorsteinsdottir U., Toniolo D., Tönjes A., Traglia M., Uda M., Ulivi S., van der Harst P., van der Schoot E., van Gilst W.H., van Pelt L.J., van Veldhuisen D.J., Verweij N., Visscher P.M., Völker U., Vollenweider P., Voss K., Wareham N.J., Wernisch L., Westra H.J., Whitfield J.B., Wichmann H.E., Wiggins K.L., Willemsen G., Winkelmann B.R., Wirnsberger G., Wolffenbuttel B.H., Yang J., Yang T.P., Zhang J.H., Zhao J.H., Zitting P., Zwaginga J.J.
ISSN
1549-5469 (Electronic)
ISSN-L
1088-9051
Publication state
Published
Issued date
07/2013
Peer-reviewed
Oui
Volume
23
Number
7
Pages
1130-1141
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits.
Keywords
Blood Platelets/metabolism, Cell Lineage/genetics, Chromatin/metabolism, Chromatin Assembly and Disassembly, Chromosome Mapping, Cluster Analysis, Erythrocytes/metabolism, Gene Expression Regulation, Genetic Variation, Genome-Wide Association Study, Histones/metabolism, Humans, Myeloid Cells/metabolism, Nucleosomes/metabolism, Organ Specificity/genetics, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Regulatory Sequences, Nucleic Acid
Pubmed
Web of science
Open Access
Yes
Create date
18/01/2021 21:44
Last modification date
19/01/2021 6:26
Usage data