Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, 92697, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Nat Commun. 2021 Jan 15;12(1):400. doi: 10.1038/s41467-020-20492-7.
Promoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity-Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.
启动子 DNA 甲基化是转录抑制的一种成熟机制，尽管它与基因表达的整体相关性很弱。这种弱相关性可以归因于当前的甲基化定量方法未能考虑到测序的大量细胞之间的异质性。在这里，我们引入了细胞异质性调整的克隆甲基化（CHALM）作为一种甲基化定量方法。CHALM 提高了对 DNA 甲基化功能后果的理解，包括其与基因表达和 H3K4me3 的相关性。当应用于不同的甲基化数据集时，CHALM 方法能够检测到具有不同生物学功能的差异甲基化基因，这些功能支持潜在的机制。
