Hepatocyte nuclear factor 4α multiple isoforms, their functions, and their interactomes

HNF4α is a master regulator gene belonging to the nuclear receptor superfamily involved in regulating a wide range of critical biological processes in different organs. Structurally, the HNF4A locus is organized with two independent promoters and is subjected to alternative splicing with the production of twelve distinct isoforms. Little is known about the mechanisms each isoform uses to regulate transcription and their biological impact, with some reports addressing these aspects. Proteomic analyses have led to identifying proteins that interact with specific HNF4α isoforms. The identification and validation of these interactions and their role in co-regulating targeted gene expression are essential to understand better the role of this transcription factor in different biological processes and pathologies. This review addresses the historical origin of HNF4α isoforms, some of the main functions of the P1 and P2 isoform subgroups and provide information on the most recent hot topic research on the nature and function of proteins associated with each of the isoforms in some biological contexts.