Search Tips

Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in chronic lymphocytic leukemia

UID: 10542

Author(s): Pastore, Alessandro*, Gaiti, Federico, Lu , Sydney X.*, Brand, Ryan M., Kulm, Scott, Huang, Kevin Y., Gu, Hongcang, Stamenova, Elena K., Chaligne, Ronan, Béguelin, Wendy, Jiang, Yanwen, Schulman, Rafael C., Kim, Kyu-Tae, Alonso, Alicia, Allan, John N., Furman, Richard R., Wu, Catherine J., Melnick, Ari M., Gnirke, Andreas, Meissner, Alexander, Bernstein, Bradley E., Abdel-Wahab, Omar Ibrahim*, Landau, Dan A. * MSK affiliated

Description
Summary from the GEO: "Cancer evolution is fueled by genetic and epigenetic diversity, and intra-tumoral heterogeneity in DNA methylation has been shown to co-operate with genetic heterogeneity to empower evolutionary capacity of cancers such as chronic lymphocytic leukemia. Here, we show that epigenetic diversification leads to decreased coordination across layers of epigenetic information, likely reflecting an admixture of cells with diverging epigenetic identities. This manifests in incomplete gene silencing by the Polycomb complex, unexpected co-occurrence of typically mutually exclusive activating and repressing histone modifications, and greater cell-to-cell transcriptional heterogeneity.
Given the importance of histone modifications to lineage plasticity in cancer15-17, intra-leukemic epigenetic heterogeneity may extend to histone modifications, likely promoting lineage plasticity by enabling permissive chromatin states. To address this question, we complemented DNAme analysis with a chromatin immunoprecipitation sequencing (ChIP-seq) compendium of histone post-translational modifications (H3K4me3, H3K27ac, H3K4me1, H3K27me3, H3K9me3 and H3K36me3) and transcriptome sequencing (RNA-seq) in a cohort of primary CLL and healthy B lymphocytes samples (CLL IGHV unmutated, n = 12; CLL IGHV mutated, n = 10; peripheral blood NBCs [CD23+CD19+CD27−IgD+], peripheral blood memory B cells [GCBs; CD23+CD19+CD27+IgD-], peripheral blood CD20+ cells."
Subject of Study
Homo sapiens
Subject(s)
DNA Methylation
Epigenetics
Leukemia, Lymphocytic, Chronic, B-Cell
OncoTree Cancer Type(s)
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Lymphoid Neoplasm
Access via GEO

TAR of BigWig and Plain Text sequencing data.
Accession #: GSE119103

Access via SRA

ChIP and RNA Sequence reads for 90 samples.
Accession #: SRP158943

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA488107

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Pastore A, Gaiti F, Lu S, et al. Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in CLL. Nature Communications. 2019; 10:1874.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Dataset Format(s)
Plain Text, SRA, TAR, BIGWIG
Dataset Size
5.2 Gb (BigWig), 3.9 Mb (Plain Text), 90 datasets ranging from 0.1 GB--5.1 GB (SRA).
Data Catalog Record Updated
2023-12-07