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SRX2281256: GSM2364551: PT_AF4_ChIPseq; Homo sapiens; ChIP-Seq
1 ILLUMINA (NextSeq 500) run: 34.1M spots, 2.7G bases, 987.1Mb downloads

Submitted by: NCBI (GEO)
Study: MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia.
show Abstracthide Abstract
Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the Mixed Lineage Leukemia (MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor prognosis leukemias. Here we find that MLL-AF4 occupies a subset of unmethylated CG-enriched genes in combination with its cofactors Menin/LEDGF and ENL. MLL-AF4 mainly displays a punctate binding pattern near gene promoters, but we also observe a second less common pattern where MLL-AF4 spreads into the gene body and is associated with increased transcription and increased histone H3 lysine 79 methylation (H3K79me2/3). Compared to other H3K79me2/3 marked genes, MLL-AF4 spreading genes are more sensitive to inhibitors of the H3K79 methyltransferase DOT1L. This sensitivity mediates synergistic interactions with additional targeted drug treatments. Therefore, epigenetic spreading and enhanced susceptibility to epidrugs provides a potential new Achilles heel for guiding combination therapies in humans. Overall design: Examination of gene expression, histone marks and multiple chromatin proteins in MLL leukemia cell lines and patient samples
Sample: PT_AF4_ChIPseq
SAMN05951179 • SRS1766340 • All experiments • All runs
Organism: Homo sapiens
Library:
Instrument: NextSeq 500
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: ChIP-seq: Fixed cells were lysed in 1% SDS lysis buffer. Samples were sonicated (~200bp) and protein-DNA complexes were isolated with antibody. Libraries were prepared according to Illumina's protocol accompanying the DNA Library Prep Master Mix Set (Part# E6040).
Experiment attributes:
GEO Accession: GSM2364551
Links:
Runs: 1 run, 34.1M spots, 2.7G bases, 987.1Mb
Run# of Spots# of BasesSizePublished
SRR447760834,092,8292.7G987.1Mb2017-01-12

ID:
3344785

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