More Like this

1. TERMINAL FLOWER 1-FD complex target genes and competition with FLOWERING LOCUS T

   https://doi.org/10.1038/s41467-020-18782-1  

   Zhu, Yang ; Klasfeld, Samantha ; Jeong, Cheol Woong ; Jin, Run ; Goto, Koji ; Yamaguchi, Nobutoshi ; Wagner, Doris ( October 2020 , Nature Communications)

   Plants monitor seasonal cues to optimize reproductive success by tuning onset of reproduction and inflorescence architecture. TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) and their orthologs antagonistically regulate these life history traits, yet their mechanism of action, antagonism and targets remain poorly understood. Here, we show that TFL1 is recruited to thousands of loci by the bZIP transcription factor FD. We identify the master regulator of floral fate,LEAFY(LFY) as a target under dual opposite regulation by TFL1 and FT and uncover a pivotal role of FT in promoting flower fate viaLFYupregulation. We provide evidence that the antagonism between FT and TFL1 relies on competition for chromatin-bound FD at shared target loci. Direct TFL1-FD regulated target genes identify this complex as a hub for repressing both master regulators of reproductive development and endogenous signalling pathways. Our data provide mechanistic insight into how TFL1-FD sculpt inflorescence architecture, a trait important for reproductive success, plant architecture and yield.

    

   more » « less
2. LEAFY and APETALA1 down-regulate ZINC FINGER PROTEIN 1 and 8 to release their repression on class B and C floral homeotic genes

   https://doi.org/10.1073/pnas.2221181120  

   Hu, Tieqiang ; Li, Xiaohui ; Du, Liren ; Manuela, Darren ; Xu, Mingli ( May 2023 , Proceedings of the National Academy of Sciences)

   Organ initiation from the shoot apical meristem first gives rise to leaves during vegetative development and then flowers during reproductive development.LEAFY(LFY) is activated after floral induction and together with other factors promotes the floral program. LFY functions redundantly with APETALA1 (AP1) to activate the class B genesAPETALA3(AP3) andPISTILLATA(PI), the class C geneAGAMOUS(AG), and the class E geneSEPALLATA3, which leads to the specification of stamens and carpels, the reproductive organs of flowers. Molecular and genetic networks that control the activation ofAP3,PI,andAGin flowers have been well studied; however, much less is known about how these genes are repressed in leaves and how their repression is lifted in flowers. Here, we showed that two genes encodingArabidopsisC2H2 ZINC FINGER PROTEIN (ZFP) transcription factors, ZP1 and ZFP8, act redundantly to directly repressAP3,PI,andAGin leaves. AfterLFYandAP1are activated in floral meristems, they down-regulateZP1andZFP8directly to lift the repression onAP3,PI,andAG. Our results reveal a mechanism for how floral homeotic genes are repressed and derepressed before and after floral induction.

    

   more » « less
3. Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding

   https://doi.org/10.1038/s41467-023-43157-7  

   Dastidar, Sayantani Ghosh ; De Kumar, Bony ; Lauckner, Bo ; Parrello, Damien ; Perley, Danielle ; Vlasenok, Maria ; Tyagi, Antariksh ; Koney, Nii Koney-Kwaku ; Abbas, Ata ; Nechaev, Sergei ( November 2023 , Nature Communications)

   Responses of cells to stimuli are increasingly discovered to involve the binding of sequence-specific transcription factors outside of known target genes. We wanted to determine to what extent the genome-wide binding and function of a transcription factor are shaped by the cell type versus the stimulus. To do so, we induced the Heat Shock Response pathway in two different cancer cell lines with two different stimuli and related the binding of its master regulator HSF1 to nascent RNA and chromatin accessibility. Here, we show that HSF1 binding patterns retain their identity between basal conditions and under different magnitudes of activation, so that common HSF1 binding is globally associated with distinct transcription outcomes. HSF1-induced increase in DNA accessibility was modest in scale, but occurred predominantly at remote genomic sites. Apart from regulating transcription at existing elements including promoters and enhancers, HSF1 binding amplified during responses to stimuli may engage inactive chromatin.

    

   more » « less
4. The nucleosome unwrapping free energy landscape defines distinct regions of transcription factor accessibility and kinetics

   https://doi.org/10.1093/nar/gkac1267  

   Donovan, Benjamin T. ; Luo, Yi ; Meng, Zhiyuan ; Poirier, Michael G. ( January 2023 , Nucleic Acids Research)

   Transcription factors (TF) require access to target sites within nucleosomes to initiate transcription. The target site position within the nucleosome significantly influences TF occupancy, but how is not quantitatively understood. Using ensemble and single-molecule fluorescence measurements, we investigated the targeting and occupancy of the transcription factor, Gal4, at different positions within the nucleosome. We observe a dramatic decrease in TF occupancy to sites extending past 30 base pairs (bp) into the nucleosome which cannot be explained by changes in the TF dissociation rate or binding site orientation. Instead, the nucleosome unwrapping free energy landscape is the primary determinant of Gal4 occupancy by reducing the Gal4 binding rate. The unwrapping free energy landscape defines two distinct regions of accessibility and kinetics with a boundary at 30 bp into the nucleosome where the inner region is over 100-fold less accessible. The Gal4 binding rate in the inner region no longer depends on its concentration because it is limited by the nucleosome unwrapping rate, while the frequency of nucleosome rewrapping decreases because Gal4 exchanges multiple times before the nucleosome rewraps. Our findings highlight the importance of the nucleosome unwrapping free energy landscape on TF occupancy and dynamics that ultimately influences transcription initiation.

    

   more » « less
5. How to scan naked DNA using promiscuous recognition and no clamping: a model for pioneer transcription factors

   https://doi.org/10.1093/nar/gkae790  

   Goluguri, Rama_Reddy ; Ghosh, Catherine ; Quintong, Joshua ; Sadqi, Mourad ; Muñoz, Victor ( September 2024 , Nucleic Acids Research)

   Most DNA scanning proteins uniquely recognize their cognate sequence motif and slide on DNA assisted by some sort of clamping interface. The pioneer transcription factors that control cell fate in eukaryotes must forgo both elements to gain access to DNA in naked and chromatin forms; thus, whether or how these factors scan naked DNA is unknown. Here, we use single-molecule techniques to investigate naked DNA scanning by the Engrailed homeodomain (enHD) as paradigm of highly promiscuous recognition and open DNA binding interface. We find that enHD scans naked DNA quite effectively, and about 200000-fold faster than expected for a continuous promiscuous slide. To do so, enHD scans about 675 bp of DNA in 100 ms and then redeploys stochastically to another location 530 bp afar in just 10 ms. During the scanning phase enHD alternates between slow- and medium-paced modes every 3 and 40 ms, respectively. We also find that enHD binds nucleosomes and does so with enhanced affinity relative to naked DNA. Our results demonstrate that pioneer-like transcription factors can in principle do both, target nucleosomes and scan active DNA efficiently. The hybrid scanning mechanism used by enHD appears particularly well suited for the highly complex genomic signals of eukaryotic cells.

    

   more » « less