Sequence-Specific Structural Features and Solvation Properties of Transcription Factor Binding DNA Motifs: Insights from Molecular Dynamics Simulation

Patra, Piya; Gao, Yi Qin

doi:10.1021/acs.jpcb.2c05749

Cited by 3 publications

(2 citation statements)

References 92 publications

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“…The JASPAR (http://jaspar.genereg.net/) database provides a comprehensive collection of transcription factor binding profiles and matrices 19 . It provides valuable insights into potential binding motifs that transcription factors may recognize within gene promoter regions 20 . In this study, the JASPAR database was used to predict the binding sites of FLRT3 and SMAD4.…”

Section: Methodsmentioning

confidence: 99%

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FLRT3 and TGF‐β/SMAD4 signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia

Pang,

Xu,

Chen

et al. 2024

J Cellular Molecular Medi

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To explore the underlying molecular mechanisms of supraventricular tachycardia (SVT), this study aimed to analyse the complex relationship between FLRT3 and TGF‐β/SMAD4 signalling pathway, which affects Na+ and K+ channels in cardiomyocytes. Bioinformatics analysis was performed on 85 SVT samples and 15 healthy controls to screen overlapping genes from the key module and differentially expressed genes (DEGs). Expression profiling of overlapping genes, coupled with Receiver Operating Characteristic (ROC) curve analyses, identified FLRT3 as a hub gene. In vitro studies utilizing Ang II‐stimulated H9C2 cardiomyocytes were undertaken to elucidate the consequences of FLRT3 silencing on cardiomyocyte apoptosis and autophagic processes. Utilizing a combination of techniques such as quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), western blotting (WB), flow cytometry, dual‐luciferase reporter assays and chromatin immunoprecipitation polymerase chain reaction (ChIP‐PCR) assays were conducted to decipher the intricate interactions between FLRT3, the TGF‐β/SMAD4 signalling cascade and ion channel gene expression. Six genes (AADAC, DSC3, FLRT3, SYT4, PRR9 and SERTM1) demonstrated reduced expression in SVT samples, each possessing significant clinical diagnostic potential. In H9C2 cardiomyocytes, FLRT3 silencing mitigated Ang II‐induced apoptosis and modulated autophagy. With increasing TGF‐β concentration, there was a dose‐responsive decline in FLRT3 and SCN5A expression, while both KCNIP2 and KCND2 expressions were augmented. Moreover, a direct interaction between FLRT3 and SMAD4 was observed, and inhibition of SMAD4 expression resulted in increased FLRT3 expression. Our results demonstrated that the TGF‐β/SMAD4 signalling pathway plays a critical role by regulating FLRT3 expression, with potential implications for ion channel function in SVT.

show abstract

Section: Methodsmentioning

confidence: 99%

“… 19 It provides valuable insights into potential binding motifs that transcription factors may recognize within gene promoter regions. 20 In this study, the JASPAR database was used to predict the binding sites of FLRT3 and SMAD4.…”

Section: Methodsmentioning

confidence: 99%

FLRT3 and TGF‐β/SMAD4 signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia

Pang,

Xu,

Chen

et al. 2024

J Cellular Molecular Medi

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Domain- and state-specific shape of the electric field tunes voltage sensing in voltage-gated sodium channels

Kostritskii

Machtens

2023

Biophysical Journal

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Structural and dynamical aspect of DNA motif sequence specific binding of AP-1 transcription factor

Patra,

Gao

2024

The Journal of Chemical Physics

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Activator protein-1 (AP-1) comprises one of the largest and most evolutionary conserved families of ubiquitous eukaryotic transcription factors that act as a pioneer factor. Diversity in DNA binding interaction of AP-1 through a conserved basic-zipper (bZIP) domain directs in-depth understanding of how AP-1 achieves its DNA binding selectivity and consequently gene regulation specificity. Here, we address the structural and dynamical aspects of the DNA target recognition process of AP-1 using microsecond-long atomistic simulations based on the structure of the human AP-1 FosB/JunD bZIP–DNA complex. Our results show the unique role of DNA shape features in selective base specific interactions, characteristic ion population, and solvation properties of DNA grooves to form the motif sequence specific AP-1–DNA complex. The TpG step at the two terminals of the AP-1 site plays an important role in the structural adjustment of DNA by modifying the helical twist in the AP-1 bound state. We addressed the role of intrinsic motion of the bZIP domain in terms of opening and closing gripper motions of DNA binding helices, in target site recognition and binding of AP-1 factors. Our observations suggest that binding to the cognate motif in DNA is mainly accompanied with the precise adjustment of closing gripper motion of DNA binding helices of the bZIP domain.

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Sequence-Specific Structural Features and Solvation Properties of Transcription Factor Binding DNA Motifs: Insights from Molecular Dynamics Simulation

Cited by 3 publications

References 92 publications

FLRT3 and TGF‐β/SMAD4 signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia

FLRT3 and TGF‐β/SMAD4 signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia

Domain- and state-specific shape of the electric field tunes voltage sensing in voltage-gated sodium channels

Structural and dynamical aspect of DNA motif sequence specific binding of AP-1 transcription factor

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