Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Proteomics. 2023 Jul;23(13-14):e2200372. doi: 10.1002/pmic.202200372. Epub 2023 May 26.
Hepatocyte nuclear factor 4-alpha (HNF4α) is a master regulator gene belonging to the nuclear receptor superfamily and is involved in regulating a wide range of critical biological processes in different organs. Structurally, the HNF4A locus is organized into two independent promoters and is subjected to alternative splicing to produce twelve distinct isoforms. However, little is known about the biological impact of each isoform and the mechanisms by which they regulate transcription. Proteomic analyses have led to the identification of proteins that interact with specific HNF4α isoforms. The identification and validation of these interactions and their roles in the co-regulation of targeted gene expression are essential to better understand the role of this transcription factor in different biological processes and pathologies. This review addresses the discoveries of different HNF4α isoforms and the main functions of the P1 and P2 isoform subgroups. It also provides information on the most recent focus areas in research on the nature and function of proteins associated with each of the isoforms in some biological contexts.
肝细胞核因子 4 阿尔法（HNF4α）是核受体超家族的一个主要调节基因，参与调节不同器官中广泛的关键生物学过程。在结构上，HNF4A 基因座组织成两个独立的启动子，并通过选择性剪接产生十二个不同的亚型。然而，对于每种亚型的生物学影响以及它们调节转录的机制知之甚少。蛋白质组学分析已经导致了与特定 HNF4α 亚型相互作用的蛋白质的鉴定。鉴定和验证这些相互作用及其在靶向基因表达的共同调节中的作用，对于更好地理解该转录因子在不同生物学过程和病理中的作用至关重要。这篇综述介绍了不同的 HNF4α 亚型的发现，以及 P1 和 P2 亚型亚组的主要功能。它还提供了有关与每个亚型相关的蛋白质的性质和功能的最新研究重点领域的信息，这些研究在一些生物学背景下进行。
