The sotos syndrome gene Nsd1 safeguards developmental gene enhancers poised for transcription by maintaining the precise deposition of histone methylation.

ABSTRACT: Germline haploinsufficiency of NSD1 is implicated as the etiology of Sotos syndrome; however, the underlying mechanism remains far from being clear. Here, we use mouse embryonic stem cell (mESC) differentiation as a model system to address this question. We found Nsd1 to be indispensable for the faithful differentiation of mESCs into three primary germ layers, particularly, meso-endodermal cell lineages related to the development of the heart and the skeletal system. Time-course transcriptomic profiling following the mESC differentiation revealed that Nsd1 not only facilitates the basal expression but also permits the differentiation-accompanied rapid induction of a suite of meso-endoderm lineage-specifying transcription factor genes such as T and Gata4. Mechanistically, Nsd1 directly occu

SUBMITTER: Li J 

PROVIDER: S-EPMC12033923 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature