WDR5 serves in co-activation and influences genome targeting of KLF3

Krüppel-like factor 3 (KLF3) is a member of the archetypal SP/KLF family of transcription factors that bind GC-rich elements and CACCC boxes in promoters and enhancers via three classical zinc fingers (ZFs) at or near their C-termini. KLF3 can both repress and activate transcription. It represses by recruiting CtBP co-repressors via its N-terminal domain but the mechanism by which it activates was unknown. Here, we show that KLF3 associates with WDR5 and this interaction is associated with gene activation. We also demonstrate that this interaction is required for proper genomic targeting of KLF3. This helps explain previous results indicating that both the C-terminal ZF DNA-binding domain and N-terminal functional domain are required for KLF3 to identify its target genes. This result adds to only a handful of examples that transcriptional co-regulators, in addition to facilitating activation and repression, can also influence target gene selection.

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Publication Details

Journal
Nucleic Acids Research
Published
2025-09-23
DOI
https://doi.org/10.1093/nar/gkaf977
Primary Topic
Kruppel-like factors research
Type
article
Field-Weighted Citation Impact
0.00

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article

WDR5 serves in co-activation and influences genome targeting of KLF3

Merlin Crossley, Mark J. Raftery, Manan Shah, Lu Yang et al.
Nucleic Acids Research
Kruppel-like factors research
article

WDR5 serves in co-activation and influences genome targeting of KLF3

Merlin Crossley, Mark J. Raftery, Manan Shah, Lu Yang, Jerene Mathews, Mahdi Haddad, Tanit Chavalit, Joel P. Mackay, Wooi Fang Lim, A.C. Spek, Marc R. Wilkins, Kate Quinlan, Ling Zhong, T. T. Vu, Vala Nejad Safari
article en

Abstract

Krüppel-like factor 3 (KLF3) is a member of the archetypal SP/KLF family of transcription factors that bind GC-rich elements and CACCC boxes in promoters and enhancers via three classical zinc fingers (ZFs) at or near their C-termini. KLF3 can both repress and activate transcription. It represses by recruiting CtBP co-repressors via its N-terminal domain but the mechanism by which it activates was unknown. Here, we show that KLF3 associates with WDR5 and this interaction is associated with gene activation. We also demonstrate that this interaction is required for proper genomic targeting of KLF3. This helps explain previous results indicating that both the C-terminal ZF DNA-binding domain and N-terminal functional domain are required for KLF3 to identify its target genes. This result adds to only a handful of examples that transcriptional co-regulators, in addition to facilitating activation and repression, can also influence target gene selection.

Nucleic Acids ResearchVol. 53(18)
The University of Sydney (AU), UNSW Sydney (AU), Bioanalytica (Switzerland) (CH)
Australian Government, University of New South Wales, China Scholarship Council
Openalex Percentile: Top 76%
Kruppel-like factors research
DOIOpen Access PDFOpenAlex
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