NSD1 mutations deregulate transcription and DNA methylation of bivalent developmental genes in Sotos syndrome.

ABSTRACT: Sotos syndrome (SS), the most common overgrowth with intellectual disability (OGID) disorder, is caused by inactivating germline mutations of NSD1, which encodes a histone H3 lysine 36 methyltransferase. To understand how NSD1 inactivation deregulates transcription and DNA methylation (DNAm), and to explore how these abnormalities affect human development, we profiled transcription and DNAm in SS patients and healthy control individuals. We identified a transcriptional signature that distinguishes individuals with SS from controls and was also deregulated in NSD1-mutated cancers. Most abnormally expressed genes displayed reduced expression in SS; these downregulated genes consisted mostly of bivalent genes and were enriched for regulators of development and neural synapse function. DNA hyp

SUBMITTER: Brennan K 

PROVIDER: S-EPMC9262396 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature