Browsing by Author "Gu, Weiliang"

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    Author Correction: Massively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation
    (Springer Nature, 2021-08-19) VanDusen, Nathan J.; Lee, Julianna Y.; Gu, Weiliang; Butler, Catalina E.; Sethi, Isha; Zheng, Yanjiang; King, Justin S.; Zhou, Pingzhu; Suo, Shengbao; Guo, Yuxuan; Ma, Qing; Yuan, Guo-Cheng; Pu, William T.; Medical and Molecular Genetics, School of Medicine
    Correction to: Nature Communications 10.1038/s41467-021-24743-z, published online 21 July 2021. The original version of this Article contained an error in the spelling of the author William T. Pu, which was incorrectly given as William William Pu. This has now been corrected in both the PDF and HTML versions of the Article.
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    Dynamic changes in P300 enhancers and enhancer-promoter contacts control mouse cardiomyocyte maturation
    (Elsevier, 2023) Zhou, Pingzhu; VanDusen, Nathan J.; Zhang, Yanchun; Cao, Yangpo; Sethi, Isha; Hu, Rong; Zhang, Shuo; Wang, Guangyu; Ye, Lincai; Mazumdar, Neil; Chen, Jian; Zhang, Xiaoran; Guo, Yuxuan; Li, Bin; Ma, Qing; Lee, Julianna Y.; Gu, Weiliang; Gupta, Weiliang; Yuan, Guo-Cheng; Ren, Bing; Chen, Kaifu; Pu, William T.; Pediatrics, School of Medicine
    Cardiomyocyte differentiation continues throughout murine gestation and into the postnatal period, driven by temporally regulated expression changes in the transcriptome. The mechanisms that regulate these developmental changes remain incompletely defined. Here, we used cardiomyocyte-specific ChIP-seq of the activate enhancer marker P300 to identify 54,920 cardiomyocyte enhancers at seven stages of murine heart development. These data were matched to cardiomyocyte gene expression profiles at the same stages and to Hi-C and H3K27ac HiChIP chromatin conformation data at fetal, neonatal, and adult stages. Regions with dynamic P300 occupancy exhibited developmentally regulated enhancer activity, as measured by massively parallel reporter assays in cardiomyocytes in vivo, and identified key transcription factor-binding motifs. These dynamic enhancers interacted with temporal changes of the 3D genome architecture to specify developmentally regulated cardiomyocyte gene expressions. Our work provides a 3D genome-mediated enhancer activity landscape of murine cardiomyocyte development.
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    Massively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation
    (Springer Nature, 2021-07-21) VanDusen, Nathan J.; Lee, Julianna Y.; Gu, Weiliang; Butler, Catalina E.; Sethi, Isha; Zheng, Yanjiang; King, Justin S.; Zhou, Pingzhu; Suo, Shengbao; Guo, Yuxuan; Ma, Qing; Yuan, Guo-Cheng; Pu, William T.; Medical and Molecular Genetics, School of Medicine
    The forward genetic screen is a powerful, unbiased method to gain insights into biological processes, yet this approach has infrequently been used in vivo in mammals because of high resource demands. Here, we use in vivo somatic Cas9 mutagenesis to perform an in vivo forward genetic screen in mice to identify regulators of cardiomyocyte (CM) maturation, the coordinated changes in phenotype and gene expression that occur in neonatal CMs. We discover and validate a number of transcriptional regulators of this process. Among these are RNF20 and RNF40, which form a complex that monoubiquitinates H2B on lysine 120. Mechanistic studies indicate that this epigenetic mark controls dynamic changes in gene expression required for CM maturation. These insights into CM maturation will inform efforts in cardiac regenerative medicine. More broadly, our approach will enable unbiased forward genetics across mammalian organ systems.