ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer.

Genome Medicine
Aileen Patricia SzczepanskiLu Wang

Abstract

Small cell lung cancer (SCLC) is a more aggressive subtype of lung cancer that often results in rapid tumor growth, early metastasis, and acquired therapeutic resistance. Consequently, such phenotypical characteristics of SCLC set limitations on viable procedural options, making it difficult to develop both screenings and effective treatments. In this study, we examine a novel mechanistic insight in SCLC cells that could potentially provide a more sensitive therapeutic alternative for SCLC patients. Biochemistry studies, including size exclusion chromatography, mass spectrometry, and western blot analysis, were conducted to determine the protein-protein interaction between additional sex combs-like protein 3 (ASXL3) and bromodomain-containing protein 4 (BRD4). Genomic studies, including chromatin immunoprecipitation sequencing (ChIP-seq), RNA sequencing, and genome-wide analysis, were performed in both human and mouse SCLC cells to determine the dynamic relationship between BRD4/ASXL3/BAP1 epigenetic axis in chromatin binding and its effects on transcriptional activity. We report a critical link between BAP1 complex and BRD4, which is bridged by the physical interaction between ASXL3 and BRD4 in an SCLC subtype (SCLC-A), which ...Continue Reading

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Citations

Aug 2, 2020·Seminars in Cancer Biology·Ammad Ahmad FarooqiMassimo Mallardo
Jan 24, 2021·Cell Death Discovery·Aileen Patricia Szczepanski, Lu Wang
Oct 28, 2020·International Journal of Molecular Sciences·Cameron J ReddingtonPeter D Mace
Apr 24, 2021·Genes & Development·Nadezda A FursovaRobert J Klose
Aug 25, 2021·Trends in Genetics : TIG·Simone TamburriDiego Pasini
Aug 31, 2021·Frontiers in Pharmacology·Yiwei ZhangXianying Fang
Aug 4, 2021·Cancer Research·Zibo ZhaoLu Wang
Sep 19, 2021·Journal of Molecular Biology·Abigail E BurgessPeter D Mace
Oct 15, 2021·Pathology Oncology Research : POR·Cuijian ZhangLiqun Zhou

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Methods Mentioned

BETA
ChIP-seq
electrophoresis
RNA-seq
ChIP
ChIPseq
PCA
co-immunoprecipitation
immunoprecipitation
transfection
pull-down

Software Mentioned

GraphPad Prism
Gene Set Enrichment Analysis
HOMER
Excel
GSEA
MACS
TreeView
CLUSTALW
DESeq2
Metascape

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