TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation

Daniil Alpern (1) , Diana Langer (1) , Benoit Ballester (2) , Stephanie Le Gras (1) , Christophe Romier (1) , Gabrielle Mengus (1) , Irwin Davidson (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 TAGC - Technologies avancées pour le génôme et la clinique

The functions of the TAF subunits of mammalian TFIID in physiological processes remain poorly characterised. In this study, we describe a novel function of TAFs in directing genomic occupancy of a transcriptional activator. Using liver-specific inactivation in mice, we show that the TAF4 subunit of TFIID is required for post-natal hepatocyte maturation. TAF4 promotes pre-initiation complex (PIC) formation at post-natal expressed liver function genes and down-regulates a subset of embryonic expressed genes by increased RNA polymerase II pausing. The TAF4–TAF12 heterodimer interacts directly with HNF4A and in vivo TAF4 is necessary to maintain HNF4A-directed embryonic gene expression at post-natal stages and promotes HNF4A occupancy of functional cis-regulatory elements adjacent to the transcription start sites of post-natal expressed genes. Stable HNF4A occupancy of these regulatory elements requires TAF4-dependent PIC formation highlighting that these are mutually dependent events. Local promoter-proximal HNF4A–TFIID interactions therefore act as instructive signals for post-natal hepatocyte differentiation.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]

Daniil Alpern, Diana Langer, Benoit Ballester, Stephanie Le Gras, Christophe Romier, et al.. TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation. eLife, 2014, 3, pp.308-312. ⟨10.7554/eLife.03613.001⟩. ⟨hal-01404987⟩