Roles of the NFI/CTF gene family in transcription and development: update 2025

This review is an update of the review entitled “Roles of the NFI/CTF gene family in transcription and development” published in Gene in 2000 (referred to hereafter as the 2000 Gene review). That review began with the sentence “The Nuclear Factor I (NFI) family of site-specific DNA-binding proteins (also known as CTF or CAAT box transcription factor) functions both in viral DNA replication and in the regulation of gene expression.”, which is as valid now as it was then. The subsequent focus of NFI research has been on the role of individual or multiple family members in gene expression during development, in various adult organ systems, and the effect of NFI mutations in human syndromes. Here we will cover post-2000 studies with an emphasis on the role of NFI genes in brain, skin, blood, skeletal muscle, and retinal development; recent studies on the effect of hemizygosity of NFI genes in human development; the role of NFI genes in cancer; and the recently described 3D structure of the NFIX DNA-binding domain.