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Linking the epigenetic landscape in chronic lymphocytic leukemia to deregulated chromatin networks

Aberrant chromatin features and epigenetic signaling emerge as an important part of the tumor disease state in chronic lymphocytic leukemia (CLL). However, an integrative analysis of the malignant chromatin landscape is currently missing. Here, we mapped DNA-methylation, nucleosome position, 7 histone modifications, ATAC-seq and the transcriptome in primary CD19+ sorted B-cells from the peripheral blood of CLL patients in comparison to non-malignant lymphocytes of healthy donor reference samples. On the > 50 kb scale we identified global differences with respect to DNA methylation, nucleosome positioning and histone modifications in CLL. Furthermore, a chromatin state annotation was developed to identify deregulated chromatin features of promoters and enhancers in CLL. By integrating these findings with an ATAC-seq based transcription factor binding analysis we identified a set of promoters and enhancers specific to CLL that were enriched in certain transcription factors binding motifs and genes of the BCR signaling pathway. Thus, our study provides an in-depth map of the CLL chromatin landscape and links chromatin state changes at promoters and enhancers to deregulated pathways.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003421 28
EGAD00001005965 Illumina HiSeq 2000 5
EGAD00001005966 Illumina HiSeq 2000 3
EGAD00001005967 Illumina HiSeq 2000 Illumina HiSeq 4000 26
EGAD00001005968 Illumina HiSeq 2000 27
EGAD00001005969 Illumina HiSeq 2000 NextSeq 550 31
EGAD00001005970 Illumina HiSeq 2000 31
Publications Citations
Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks.
Mol Syst Biol 15: 2019 e8339
Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL.
Genome Med 12: 2020 29
A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation.
Nat Commun 13: 2022 2042
Nucleosome repositioning in chronic lymphocytic leukemia.
Genome Res 33: 2023 1649-1661