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Establishment and maintenance of active or inactive chromatin states are fundamental processes in metazoan biology. In mammals, two well-known classes of epigenetic gene silencing are imprinting and X chromosome inactivation (XCI). Our research has shown that each pair of autosomes has multiple loci behaving in a manner similar to XCI.
Research in the laboratory is focused on the questions concerning allele-specific reguation of gene expression, particularly in the genes subject to "random" monoallelic expression (MAE).
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News:
(2/18/2020) Posted on bioRxiv:
Unexpected variability of allelic imbalance estimates from RNA sequencing
Asia Mendelevich, Svetlana Vinogradova, Saumya Gupta, Andrey A. Mironov, Shamil Sunyaev, Alexander A. Gimelbrant
bioRxiv 2020.02.18.948323doi: https://doi.org/10.1101/2020.02.18.948323We report that current approaches to allele-specific expression analysis underestimate technical noise and can lead to false positives. To measure allele-specific signal accurately, make technical replicates of RNA-seq libraries, and use them to calculate allelic overdispersion. R package: github.com/gimelbrantlab/Qllelic
(2/20/2020) Posted on bioRxiv:
Mechanism of monoallelic expression and allelic rheostat role of DNA methylation
Saumya Gupta, Denis L. Lafontaine, [...], Anwesha Nag, Alexander A. Gimelbrant
bioRxiv 2020.02.20.954834; doi: https://doi.org/10.1101/2020.02.20.954834Thousands of mammalian genes are subject to autosomal monoallelic expression (MAE), but the mechanism of MAE mitotic maintenance has been unknown. We designed a new screening-by-sequencing strategy to find perturbations that can change allelic imbalance. In contrast to previous reports, we find that DNA methylation precisely controls allelic imbalance for MAE and other genes.
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