NCOR1 modulates erythroid disorders caused by mutations of thyroid hormone receptor α1.

ABSTRACT: Thyroid hormone receptor α (THRA) gene mutations, via dominant negative mode, cause erythroid abnormalities in patients. Using mice expressing a dominant negative TRα1 mutant (TRα1PV; Thra1 PV/+ mice), we showed that TRα1PV acted directly to suppress the expression of key erythroid genes, causing erythroid defects. The nuclear receptor corepressor 1 (NCOR1) was reported to mediate the dominant negative effects of mutated TRα1. However, how NCOR1 could regulate TRα1 mutants in erythroid defects in vivo is not known. In the present study, we crossed Thra1 PV/+ mice with mice expressing a mutant Ncor1 allele (NCOR1ΔID; Ncor1 ΔID mice). TRα1PV mutant cannot bind to NCOR1ΔID. The expression of NCOR1ΔID ameliorated abnormalities in the peripheral blood indices, and corrected the defective differ

SUBMITTER: Han CR 

PROVIDER: S-EPMC5741760 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature