Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V38
Höfundar / Authors: Magnús Arnar Rúnarsson, Pétur Orri Heiðarsson og Kristinn Ragnar Óskarsson
Starfsvettvangur / Affiliations: Háskóli Íslands
Kynnir / Presenter: Kristinn Ragnar Óskarsson
FOXA1 is a pioneer transcription factor with chromatin remodeling activity and is also a key regulator of hormone nuclear receptors in various tissues. FOXA1 also plays a critical role in the progression and prognosis of nuclear receptor positive cancers that develop in the mammary gland and prostate. The central domain in FOXA1, the DNA binding domain (DBD), has been extensively studied, with its structure and function mostly resolved. However, its intrinsically disordered regions (IDRs), the N- and C-terminus, remain poorly understood. In this study, we investigated the structure and dynamics of full-length and truncated variants of FOXA1 with a focus on its disordered regions. Using single-molecule FRET, we mapped the dynamic properties of FOXA1 IDRs. Our results confirm that both termini are disordered and highly dynamic. Experiments of truncated FOXA1 variants indicate that the two IDRs of FOXA1 influence each other, as the removal of one can cause structural and functional changes in the counterpart. We found that the termini might work together to modulate DNA binding, likely through interactions with the DBD. These results suggest that the N- and C-IDRs in FOXA1 play active roles in regulating DNA binding and potentially its pioneering activity.