Chromatin accessibility maps of chronic lymphocytic leukemia identify subtypespecific epigenome signatures and associated transcription regulatory networks
Chromatin accessibility maps of chronic lymphocytic leukemia identify subtypespecific epigenome signatures and associated transcription regulatory networks
Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay. These data were further complemented by ChIPmentation and RNA-seq profiling in ten samples. Based on this dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic regulatory differences between these two disease subtypes. In summary, we found widespread heterogeneity in the CLL chromatin landscape, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.
1-25
Rendeiro, Andre F.
5ef189ac-b1d9-40bf-b731-6f438c948e79
Schmidl, Christian
2d6616b6-748e-4c66-a72a-48a53909c092
Strefford, Jonathan C.
8c942ae3-009a-492c-9c74-9b42957f6487
Walewska, Renata
326c1001-fcdb-452a-aa53-2c82a1ca39a5
Davis, Zadie
ea848a46-b564-448f-b77f-840d86b3cbd9
Farlik, Matthias
6f91d823-4c40-466e-87d7-fe30ec7673c5
Oscier, David
c2620a1d-25bb-48f7-9651-f5d023636381
Bock, Christoph
db9a1e5d-09ae-458f-9e86-3a02cdf00bed
Rendeiro, Andre F.
5ef189ac-b1d9-40bf-b731-6f438c948e79
Schmidl, Christian
2d6616b6-748e-4c66-a72a-48a53909c092
Strefford, Jonathan C.
8c942ae3-009a-492c-9c74-9b42957f6487
Walewska, Renata
326c1001-fcdb-452a-aa53-2c82a1ca39a5
Davis, Zadie
ea848a46-b564-448f-b77f-840d86b3cbd9
Farlik, Matthias
6f91d823-4c40-466e-87d7-fe30ec7673c5
Oscier, David
c2620a1d-25bb-48f7-9651-f5d023636381
Bock, Christoph
db9a1e5d-09ae-458f-9e86-3a02cdf00bed
Rendeiro, Andre F., Schmidl, Christian, Strefford, Jonathan C., Walewska, Renata, Davis, Zadie, Farlik, Matthias, Oscier, David and Bock, Christoph
(2016)
Chromatin accessibility maps of chronic lymphocytic leukemia identify subtypespecific epigenome signatures and associated transcription regulatory networks.
Nature Communications, .
(In Press)
Abstract
Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay. These data were further complemented by ChIPmentation and RNA-seq profiling in ten samples. Based on this dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic regulatory differences between these two disease subtypes. In summary, we found widespread heterogeneity in the CLL chromatin landscape, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.
Text
__soton.ac.uk_ude_personalfiles_users_jcs_mydesktop_82766_1_merged_1458417673.pdf
- Accepted Manuscript
More information
Accepted/In Press date: 7 May 2016
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 394140
URI: http://eprints.soton.ac.uk/id/eprint/394140
PURE UUID: c56c77ab-9c0b-478b-8760-65dcfce1e7c2
Catalogue record
Date deposited: 12 May 2016 09:21
Last modified: 15 Mar 2024 05:34
Export record
Contributors
Author:
Andre F. Rendeiro
Author:
Christian Schmidl
Author:
Jonathan C. Strefford
Author:
Renata Walewska
Author:
Zadie Davis
Author:
Matthias Farlik
Author:
David Oscier
Author:
Christoph Bock
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics