Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture
UID: 10591
- Description
- Summary from the GEO: "Linker histone H1 proteins bind to nucleosomes and cause chromatin compaction, although little is known about their biological functions. Histone H1 (HIST1H1B-E) mutations are highly recurrent in B-cell lymphomas and are present in solid tumors, but their cancer relevance and mechanism are unknown. Here we report that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. H1 mutations disrupt their ability to bind or compact chromatin. This causes profound architectural remodeling of the genome characterized by large-scale, yet focal shifts of chromatin from a compacted, to a relaxed state. The degree of decompaction results in distinct epigenetic states, primarily due to gain of histone H3 lysine 36 dimethylation, and/or loss of repressive H3K27 methylation. These changes unlock expression of stem cell genes that are normally silenced during early development. Loss of H1c and H1e alleles in mice conferred enhanced fitness and self renewal properties to germinal center B-cells, ultimately leading to aggressive lymphoma with enhanced repopulating potential. Collectively, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We furthermore establish H1 as a bona fide tumor suppressor, whose mutation drives malignant transformation primarily through three-dimensional genome reorganization, epigenetic reprogramming and aberrant de-repression of developmentally silenced genes."
Overall design from the GEO: "RNA-seq, ChIP-seq, Cut&Run, ATAC-seq, and HiC sequencing data in HIST1H1C- and HIST1H1E-deficient germinal center B cells"
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Access via GEO
HIC, MTX, TSV, TXT files of expression profiling by high throughput sequencing
Accession #: GSE143293Access via SRASequencing for 53 samples
Accession #: SRP240350Access via BioProjectAdditional information about overall initiative.
Accession #: PRJNA599930 - Access Restrictions
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Free to All
- Access Instructions
- The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
- Associated Publications
- Data Type
- Equipment Used
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Illumina NovaSeq 6000
- Dataset Format(s)
- Plain Text, TSV, SRA, TAR, HIC, MTX
- Dataset Size
- 4.3 GB (TAR of HIC, MTX, TSV, TXT), 353.2 Gb (SRA)
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