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Article Abstract
Undefined epigenetic programs act to probabilistically silence individual autosomal alleles, generating unique individuals, even from genetic clones. This sort of random monoallelic expression can explain variation in traits and diseases that differences in genes and environments cannot. Here, we developed the nematode to study monoallelic expression in whole tissues, and defined a developmental genetic regulation pathway. We found maternal H3K9 histone methyltransferase (HMT) SET-25/SUV39/G9a works with HPL-2/HP1 and LIN-61/L3MBTL2 to randomly silence alleles in the intestinal progenitor E-cell of 8-cell embryos to cause monoallelic expression. SET-25 was antagonized by another maternal H3K9 HMT, MET-2/SETDB1, which works with LIN-65/ATF7ZIP and ARLE-14/ARL14EP to prevent monoallelic expression. The HMT-catalytic SET domains of both MET-2 and SET-25 were required for regulating monoallelic expression. Our data support a model wherein SET-25 and MET-2 regulate histones during development to generate patterns of somatic monoallelic expression that are persistent but not heritable.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849558 | PMC |
| http://dx.doi.org/10.1101/2024.01.22.576748 | DOI Listing |
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