5DUI

Identification of a new FoxO1 binding site that precludes CREB binding at the glucose-6-phosphatase catalytic subunit gene promoter

Summary for 5DUI

• Entry DOI: 10.2210/pdb5dui/pdb
• Descriptor: Forkhead box protein O1, DNA (5'-D(*TP*TP*TP*TP*CP*TP*AP*TP*TP*TP*TP*AP*CP*GP*TP*AP*AP*AP*TP*CP*A)-3'), DNA (5'-D(*AP*TP*GP*AP*TP*TP*TP*AP*CP*GP*TP*AP*AP*AP*AP*TP*AP*GP*AP*AP*A)-3'), ... (4 entities in total)
• Functional Keywords: transcription factor, winged helix, dna binding, protein-dna complex, diabetes, transcription regulation, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : Q12778
• Total number of polymer chains: 4
• Total formula weight: 37771.29

Authors

Singh, P.,Endrizzi, J.A.,Chi, Y.-I. (deposition date: 2015-09-18, release date: 2016-09-21, Last modification date: 2023-09-27)

Primary citation

Singh, P.,Han, E.H.,Endrizzi, J.A.,O'Brien, R.M.,Chi, Y.I.
Crystal structures reveal a new and novel FoxO1 binding site within the human glucose-6-phosphatase catalytic subunit 1 gene promoter.
J. Struct. Biol., 198:54-64, 2017

PubMed Abstract: Human glucose-6-phosphatase plays a vital role in blood glucose homeostasis and holds promise as a therapeutic target for diabetes. Expression of its catalytic subunit gene 1 (G6PC1) is tightly regulated by metabolic-response transcription factors such as FoxO1 and CREB. Although at least three potential FoxO1 binding sites (insulin response elements, IREs) and one CREB binding site (cAMP response element, CRE) within the proximal region of the G6PC1 promoter have been identified, the interplay between FoxO1 and CREB and between FoxO1 bound at multiple IREs has not been well characterized. Here we present the crystal structures of the FoxO1 DNA binding domain in complex with the G6PC1 promoter. These complexes reveal the presence of a new non-consensus FoxO1 binding site that overlaps the CRE, suggesting a mutual exclusion mechanism for FoxO1 and CREB binding at the G6PC1 promoter. Additional findings include (i) non-canonical FoxO1 recognition sites, (ii) incomplete FoxO1 occupancies at the available IRE sites, and (iii) FoxO1 dimeric interactions that may play a role in stabilizing DNA looping. These findings provide insight into the regulation of G6PC1 gene transcription by FoxO1, and demonstrate a high versatility of target gene recognition by FoxO1 that correlates with its diverse roles in biology.

PubMed: 28223045
DOI: 10.1016/j.jsb.2017.02.006

Experimental method

X-RAY DIFFRACTION (2.306 Å)