H3K4me3
生物
表观遗传学
组蛋白
染色质
组蛋白H3
遗传学
组蛋白密码
表观遗传学
染色质免疫沉淀
基因
癌症研究
计算生物学
发起人
DNA甲基化
基因表达
核小体
作者
Camila López,Mohammad T. Barnon,Tasnim H. Beacon,Gino Nardocci,James R. Davie
出处
期刊:Gene
[Elsevier]
日期:2022-06-01
卷期号:826: 146463-146463
被引量:9
标识
DOI:10.1016/j.gene.2022.146463
摘要
Epigenetic processes are radically altered in cancer cells. The altered epigenetic events may include histone post-translational modifications (PTMs), DNA modifications, and/or alterations in the levels and modifications of chromatin modifying enzymes and chromatin remodelers. With changes in gene programming are changes in the genomic distribution of histone PTMs. Genes that are poised or transcriptionally active have histone H3 trimethylated lysine 4 (H3K4me3) located at the transcription start site and at the 5′ end of the gene. However, a small population of genes that are involved in cell identity or cancer cell properties have a broad H3K4me3 domain that may stretch for several kilobases through the coding region of the gene. Each cancer cell type appears to mark a select set of cancer-related genes in this manner. In this study, we determined which genes were differentially marked with the broad H3K4me3 domain in normal-like (MCF10A), luminal-type breast cancer (MCF7), and triple-negative breast cancer (MDA-MB-231) cells. We also determined whether histone H3 acetylated lysine 4 (H3K4ac), also a mark of active promoters, had a broad domain configuration. We applied two peak callers (MACS2, PeakRanger) to analyze H3K4me3 and H3K4ac chromatin immunoprecipitation sequencing (ChIP-Seq) data. We identified genes with a broad H3K4me3 and/or H3K4ac domain specific to each cell line and show that the genes have critical roles in the breast cancer subtypes. Furthermore, we show that H3K4ac marks enhancers. The identified genes with the broad H3K4me3/H3K4ac domain have been targeted in clinical and pre-clinical studies including therapeutic treatments of breast cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI