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LOXL2-mediated chromatin compaction is required to maintain the oncogenic properties of triple-negative breast cancer cells

ABSTRACT: Oxidation of histone H3 at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase–like 2 (LOXL2). This histone modification is enriched in heterochromatin in triple-negative breast cancer (TNBC) cells and has been linked to the maintenance of compacted chromatin. However, the molecular mechanism underlying this maintenance is still unknown. Here we show that LOXL2 interacts with RUVBL1, RUVBL2, BAF53, and DMAP1, a complex involved in the incorporation of the histone variant H2A.Z. Our experiments indicate that this interaction and the active form of RUVBL2 are required to maintain LOXL2-dependent chromatin compaction. Genome-wide experiments showed that H2A.Z, RUVBL2, and H3K4ox colocalize in heterochromatin regions. In the absence of LOXL2 or RUVBL2, global levels of the heterochromatin histone mark H3K9me3 were strongly reduced, and the ATAC-seq signal in the H3K9me3 regions was increased. Finally, we observed that the interplay between these series of events is required to maintain H3K4ox-enriched heterochromatin regions, which in turn is key for maintaining the oncogenic properties of the TNBC cell line tested (MDA-MB-231).

ORGANISM(S): Homo sapiens

PROVIDER: GSE142463 | GEO | 2023/12/31

REPOSITORIES: GEO

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Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple-negative breast cancer

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LSD1 Prevents Aberrant Heterochromatin Formation in Neurospora crassa

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LOXL2 dependent genes in RA induced mES differentiation

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H3K4ox-Mediated Chromatin Condensation Protects Breast Cancer Cells from the DNA Damage Repair Machinery

Project description:Using an H3K4ox-specific antibody, we determined that the H3K4ox modification is enriched in triple-negative breast cancer (TNBC) cells compared with luminal breast cancer subtypes—correlating with high LOXL2 levels— and, importantly, is found primarily in heterochromatin.

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Loss of H3K9me3 heterochromatin at protein coding genes enables developmental lineage specification (ChIP-Seq)

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2018-10-31 | GSE114196 | GEO

Loss of H3K9me3 heterochromatin at protein coding genes enables developmental lineage specification (RNA-Seq)

2018-10-31 | GSE114195 | GEO

Loss of H3K9me3 heterochromatin at protein coding genes enables developmental lineage specification (srHC-seq)

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LOXL2 dependent genes in RA induced mES differentiation

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A novel Lysyl oxidase like 2 alternative splicing LOXL2 â³e13 in esophageal squamous carcinoma cells

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2016-07-03 | E-GEOD-53676 | biostudies-arrayexpress

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