Disrupted transcriptional networks regulated by CHD1L during neurodevelopment underlie the mirrored neuroanatomical and growth phenotypes of the 1q21.1 copy number variant.

ABSTRACT: Distal 1q21.1 deletions and duplications are associated with variable phenotypes including autism, head circumference and height defects. To elucidate which gene(s) are responsible for the 1q21.1 duplication/deletion-associated phenotypes, we performed gene manipulation in zebrafish and mice. We modeled 1q21.1 duplication by overexpressing the eight human protein-coding genes in zebrafish. We found that only overexpression of CHD1L led to macrocephaly and increased larval body length, whereas chd1l deletion caused opposite phenotypes. These mirrored phenotypes were also observed in mouse embryos. Transcriptomic, cistromic, and chromatin accessibility analyses of CHD1L knock-out hiPSC-derived neuronal progenitor cells revealed that CHD1L regulates the expression levels and chromatin accessi

SUBMITTER: Lemee MV 

PROVIDER: S-EPMC12456972 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature