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| Status |
Public on Dec 31, 2023 |
| Title |
LOXL2-mediated chromatin compaction is required to maintain the oncogenic properties of triple-negative breast cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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).
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| Overall design |
ChIP-seq (5 samples), RNA-seq (8 samples) and ATAC-seq (2 samples) of MDA-MB-231 cells. shControl means shRNA Control, shLOXL2 means knock-down of LOXL2 and shRUVBL2 means know knock-down of RUVBL2.
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| Contributor(s) |
Serra-Bardenys G, Peiró S, Blanco E |
| Citation(s) |
38451841 |
| |
| Submission date |
Dec 20, 2019 |
| Last update date |
Apr 02, 2024 |
| Contact name |
Enrique Blanco |
| E-mail(s) |
[email protected]
|
| Phone |
+34 93 316 01 00
|
| Organization name |
Center for Genomic Regulation (CRG)
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| Department |
Gene Regulation, Stem Cells and Cancer
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| Lab |
Epigenetic Events in Cancer (L. Di Croce's lab)
|
| Street address |
Dr. Aiguader 88
|
| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA597060 |
| SRA |
SRP238427 |
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