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- W3178024099 endingPage "2239" @default.
- W3178024099 startingPage "2225" @default.
- W3178024099 abstract "Abstract Oligodendrocytes (OLs) produce myelin in the central nervous system (CNS), which accelerates the propagation of action potentials and supports axonal integrity. As a major component of CNS myelin, proteolipid protein 1 (Plp1) is indispensable for the axon-supportive function of myelin. Notably, this function requires the continuous high-level expression of Plp1 in OLs. Equally important is the controlled expression of Plp1, as illustrated by Pelizaeus–Merzbacher disease for which the most common cause is PLP1 overexpression. Despite a decade-long search, promoter–distal OL enhancers that govern Plp1 remain elusive. We have recently developed an innovative method that maps promoter–distal enhancers to genes in a principled manner. Here, we applied it to Plp1, uncovering two OL enhancers for it (termed Plp1-E1 and Plp1-E2). Remarkably, clustered regularly interspaced short palindromic repeats (CRISPR) interference epigenome editing showed that Plp1-E1 and Plp1-E2 do not regulate two genes in their vicinity, highlighting their exquisite specificity to Plp1. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) data show that Plp1-E1 and Plp1-E2 are OL-specific enhancers that are conserved among human, mouse and rat. Hi-C data reveal that the physical interactions between Plp1-E1/2 and PLP1 are among the strongest in OLs and specific to OLs. We also show that Myrf, a master regulator of OL development, acts on Plp1-E1 and Plp1-E2 to promote Plp1 expression." @default.
- W3178024099 created "2021-07-19" @default.
- W3178024099 creator A5008599536 @default.
- W3178024099 creator A5033081122 @default.
- W3178024099 creator A5075973162 @default.
- W3178024099 creator A5076008888 @default.
- W3178024099 date "2021-07-06" @default.
- W3178024099 modified "2023-10-15" @default.
- W3178024099 title "Identifying oligodendrocyte enhancers governing <i>Plp1</i> expression" @default.
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- W3178024099 doi "https://doi.org/10.1093/hmg/ddab184" @default.