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Title: Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
Author: Speedy, Helen E.
Beekman, Renée
Chapaprieta, Vicente
Orlando, Giulia
Law, Philip J.
Martín García, David
Gutiérrez-Abril, Jesús
Catovsky, Daniel
Beà Bobet, Sílvia M.
Clot, Guillem
Puiggròs, Montserrat
Torrents Arenales, David
Puente, Xose S.
Allan, James M.
López-Otin, Carlos
Campo Güerri, Elias
Houlston, Richard S.
Martín-Subero, José Ignacio
Keywords: Epigènesi
Leucèmia limfocítica crònica
Cèl·lules B
Chronic lymphocytic leukemia
B cells
Issue Date: 9-Aug-2019
Publisher: Nature Publishing Group
Abstract: Genome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk loci in up to 486 primary CLLs. We identify that risk loci are significantly enriched for active chromatin in CLL with evidence of being CLL-specific or differentially regulated in normal B-cell development. We then use in situ promoter capture Hi-C, in conjunction with gene expression data to reveal likely target genes of the risk loci. Candidate target genes are enriched for pathways related to B-cell development such as MYC and BCL2 signalling. At 14 loci the analysis highlights 63 variants as the probable functional basis of CLL risk. By integrating genetic and epigenetic information our analysis reveals novel insights into the relationship between inherited predisposition and the regulatory chromatin landscape of CLL.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2019, vol. 10, num. 1, p. 3615
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Fonaments Clínics)

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