License to flower: LEAFY has pioneer activity

Abstract

The transition to reproductive development is a key step in the lifecycle of a plant and requires fine-tuning of gene expression through the concerted action of several transcription factors (TFs). While most TFs bind naked DNA (without nucleosomes) in a sequence-specific manner, in mammals a special group with key roles in cell fate reprogramming, named pioneer TFs, can bind nucleosome-occupied DNA. In Arabidopsis, LEAFY (LFY) promotes floral fate through activation of floral homeotic genes (Parcy et al., 1998Parcy F. Nilsson O. Busch M.A. Lee I. Weigel D. A genetic framework for floral patterning.Nature. 1998; 395: 561-566Crossref PubMed Scopus (405) Google Scholar), some of which are targeted by the Polycomb Repressive Complex 2 and localize to closed chromatin environments. Hence, LFY has been proposed to act as a pioneer TF, but whether/how it can bind occluded DNA remained unknown. Recently, Jin et al., 2021Jin R. Klasfeld S. Zhu Y. Garcia M.F. Xiao J. Han S.-K. Konkol A. Wagner D. LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate.Nat. Comms. 2021; 12: 626Crossref PubMed Scopus (19) Google Scholar and Lai et al., 2021Lai X. Blanc-Mathieu R. GrandVuillemin L. Huang Y. Stigliani A. Lucas J. Thévenon E. Loue-Manifel J. Turchi L. Daher H. et al.The LEAFY floral regulator displays pioneer transcription factor properties.Mol. Plant. 2021; https://doi.org/10.1016/j.molp.2021.03.004Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar have analyzed public MNase and chromatin immunoprecipitation sequencing datasets and identified LFY binding sites close to the nucleosome midpoint at a sub-set of floral regulators. LFY binding to nucleosome-occupied DNA was further validated by electrophoretic mobility shift assay using in-vitro-assembled nucleosomes (Jin et al., 2021Jin R. Klasfeld S. Zhu Y. Garcia M.F. Xiao J. Han S.-K. Konkol A. Wagner D. LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate.Nat. Comms. 2021; 12: 626Crossref PubMed Scopus (19) Google Scholar; Lai et al., 2021Lai X. Blanc-Mathieu R. GrandVuillemin L. Huang Y. Stigliani A. Lucas J. Thévenon E. Loue-Manifel J. Turchi L. Daher H. et al.The LEAFY floral regulator displays pioneer transcription factor properties.Mol. Plant. 2021; https://doi.org/10.1016/j.molp.2021.03.004Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar), analysis of genome-wide nucleosome occupancy before and after LFY binding, and LFY-H3 sequential chromatin immunoprecipitation at the APETALA1 (AP1) locus (Jin et al., 2021Jin R. Klasfeld S. Zhu Y. Garcia M.F. Xiao J. Han S.-K. Konkol A. Wagner D. LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate.Nat. Comms. 2021; 12: 626Crossref PubMed Scopus (19) Google Scholar). Moreover, DNA affinity purification sequencing using both methylated and non-methylated DNA showed that LFY binding is only moderately affected by methylation and can be enhanced when specific cytosines are methylated (Lai et al., 2021Lai X. Blanc-Mathieu R. GrandVuillemin L. Huang Y. Stigliani A. Lucas J. Thévenon E. Loue-Manifel J. Turchi L. Daher H. et al.The LEAFY floral regulator displays pioneer transcription factor properties.Mol. Plant. 2021; https://doi.org/10.1016/j.molp.2021.03.004Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar). Thus, LFY can bind targets in closed chromatin contexts, displaying pioneer activity. However, this capacity seems to be limited, as higher states of chromatin compaction were not detected among LFY in vivo targets (Lai et al., 2021Lai X. Blanc-Mathieu R. GrandVuillemin L. Huang Y. Stigliani A. Lucas J. Thévenon E. Loue-Manifel J. Turchi L. Daher H. et al.The LEAFY floral regulator displays pioneer transcription factor properties.Mol. Plant. 2021; https://doi.org/10.1016/j.molp.2021.03.004Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar). Another key feature of pioneer TFs is the ability to promote local chromatin opening, either directly or through the recruitment of chromatin remodelers, and therefore allow binding of additional regulators. Accordingly, LFY binding to AP1 in a nucleosome context recruited a subunit of a chromatin remodeling SWI/SNF complex, increasing DNA accessibility locally through reduction of nucleosome and linker histone H1 occupancy (Figure 1; Jin et al., 2021Jin R. Klasfeld S. Zhu Y. Garcia M.F. Xiao J. Han S.-K. Konkol A. Wagner D. LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate.Nat. Comms. 2021; 12: 626Crossref PubMed Scopus (19) Google Scholar). Local opening of the chromatin was observed in vivo upon floral induction through LFY ectopic expression in seedlings (Lai et al., 2021Lai X. Blanc-Mathieu R. GrandVuillemin L. Huang Y. Stigliani A. Lucas J. Thévenon E. Loue-Manifel J. Turchi L. Daher H. et al.The LEAFY floral regulator displays pioneer transcription factor properties.Mol. Plant. 2021; https://doi.org/10.1016/j.molp.2021.03.004Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar) and root explants (Jin et al., 2021Jin R. Klasfeld S. Zhu Y. Garcia M.F. Xiao J. Han S.-K. Konkol A. Wagner D. LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate.Nat. Comms. 2021; 12: 626Crossref PubMed Scopus (19) Google Scholar), highlighting its relevance in floral fate determination. The ability to bind occluded DNA is likely not exclusive to LFY and has been suggested for other TFs involved in floral and seed development. However, the properties that distinguish a pioneer TF from others remain poorly understood. Both groups showed that LFY binds in a sequence-specific manner to only one side of the DNA helix, a feature shared with some mammalian pioneer TFs. However, LFY-induced changes in chromatin accessibility are not always immediate and do not occur at all target genes, suggesting that additional factors may regulate TF binding in a nucleosome context. Future work is needed to address this possibility and unveil exciting new aspects of TF regulation in plants. No conflict of interest declared.