The chromatin-remodeling enzyme CHD3 plays a role in embryonic viability but is dispensable for early vascular development.

ABSTRACT: ATP-dependent chromatin-remodeling complexes epigenetically modulate transcription of target genes to impact a variety of developmental processes. Our lab previously demonstrated that CHD4-a central ATPase and catalytic enzyme of the NuRD chromatin-remodeling complex-plays an important role in murine embryonic endothelial cells by transcriptionally regulating vascular integrity at midgestation. Since NuRD complexes can incorporate the ATPase CHD3 as an alternative to CHD4, we questioned whether the CHD3 enzyme likewise modulates vascular development or integrity. We generated a floxed allele of Chd3 but saw no evidence of lethality or vascular anomalies when we deleted it in embryonic endothelial cells in vivo (Chd3ECKO). Furthermore, double-deletion of Chd3 and Chd4 in embryonic endothelial cells (Chd3/4ECKO) did not dramatically alter the timing and severity of embryonic phenotypes seen in Chd4ECKO mutants, indicating that CHD3 does not play a cooperative role with CHD4 in early vascular development. However, excision of Chd3 at the epiblast stage of development with a Sox2-Cre line allowed us to generate global heterozygous Chd3 mice (Chd3?/+), which were subsequently intercrossed and revealed partial lethality of Chd3?/? mutants prior to weaning. Tissues from surviving Chd3?/? mutants helped us confirm that CHD3 was efficiently deleted in these animals and that CHD3 is highly expressed in the gonads and brains of adult wildtype mice. Therefore, Chd3-flox mice will be beneficial for future studies about roles for this chromatin-remodeling enzyme in viable embryonic development and in gonadal and brain physiology.

SUBMITTER: Xie J 

PROVIDER: S-EPMC7357745 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature