DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts

Yasuaki Enoki (1) , Yuka Mukoda (1) , Chie Furutani (1) , Hiroshi Sakurai (1)

1 Division of Health Sciences

Heat shock transcription factor HSF4 is necessary for ocular lens development and fiber cell differentiation. Mutations of the human gene have been implicated in congenital and age-related cataracts. Here, we show that HSF4 activates transcription of genes encoding crystallins and beaded filament structural proteins in lens epithelial cells. Five missense mutations that have been associated with congenital cataract inhibited DNA binding of HSF4, which demonstrates the relationship between mutations, loss of lens protein gene expression, and cataractogenesis. However, two missense mutations that have been associated with age-related cataract did not or only slightly alter HSF4 activity, implying that other genetic and environmental factors affect the functions of these mutant proteins.

Mots clés: HSF4; congenital cataract; age-related cataract; crystallin; beaded filament structural protein

Yasuaki Enoki, Yuka Mukoda, Chie Furutani, Hiroshi Sakurai. DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010, 1802 (9), pp.749. ⟨10.1016/j.bbadis.2010.06.001⟩. ⟨hal-00609000⟩