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Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.


ABSTRACT: Cells and tissues have a remarkable ability to adapt to genetic perturbations via a variety of molecular mechanisms. Nonsense-induced transcriptional compensation, a form of transcriptional adaptation, has recently emerged as one such mechanism, in which nonsense mutations in a gene can trigger upregulation of related genes, possibly conferring robustness at cellular and organismal levels. However, beyond a handful of developmental contexts and curated sets of genes, to date, no comprehensive genome-wide investigation of this behavior has been undertaken for mammalian cell types and contexts. Moreover, how the regulatory-level effects of inherently stochastic compensatory gene networks contribute to phenotypic penetrance in single cells remains unclear. Here we combine computational analys

SUBMITTER: Mellis IA 

PROVIDER: S-EPMC10462021 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature