DNA–Protein Binding is Dominated by Short Anchoring Elements

Abstract Unveiling the complexities of gene expression regulation, the study explores the intricate DNA‐binding mechanisms of transcription factors (TFs). By employing the KaScape method previously developed to measure both bound and unbound populations at thermodynamic equilibrium, “anchoring eleme...

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Main Authors: Hong Chen, Yongping Xu, Hao Ge, Xiao‐Dong Su
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202414823
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author Hong Chen
Yongping Xu
Hao Ge
Xiao‐Dong Su
author_facet Hong Chen
Yongping Xu
Hao Ge
Xiao‐Dong Su
author_sort Hong Chen
collection DOAJ
description Abstract Unveiling the complexities of gene expression regulation, the study explores the intricate DNA‐binding mechanisms of transcription factors (TFs). By employing the KaScape method previously developed to measure both bound and unbound populations at thermodynamic equilibrium, “anchoring elements” (AEs), 3–4 base pair sequences, are identified in Arabidopsis WRKY and human PU.1 TFs crucial for binding affinity. Building on the BEESEM method, the study introduces the AEEscape algorithm, which advances the AE concept by creating a precise model of the position‐specific k‐mer binding energy landscape. This method allows for the direct identification of the dominant role of AEs from experimental data. Moreover, when integrated with genomic data, it reveals an energetic funnel around transcription factor binding sites (TFBSs), which is directly correlated with the density of AEs (AED). The findings not only offer a fresh perspective on TF‐TFBS interactions but also highlight the critical role of AED in gene regulation. These insights can pave the way for innovative strategies to manipulate gene expression.
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publishDate 2025-05-01
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spelling doaj-art-a256d19b72fa4a7e8b646d1d7c6b6a902025-08-20T01:52:42ZengWileyAdvanced Science2198-38442025-05-011219n/an/a10.1002/advs.202414823DNA–Protein Binding is Dominated by Short Anchoring ElementsHong Chen0Yongping Xu1Hao Ge2Xiao‐Dong Su3State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC) Peking University Beijing 100871 ChinaState Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC) Peking University Beijing 100871 ChinaBeijing International Center for Mathematical Research (BICMR) and Biomedical Pioneering Innovation Center (BIOPIC) Peking University Beijing 100871 ChinaState Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC) Peking University Beijing 100871 ChinaAbstract Unveiling the complexities of gene expression regulation, the study explores the intricate DNA‐binding mechanisms of transcription factors (TFs). By employing the KaScape method previously developed to measure both bound and unbound populations at thermodynamic equilibrium, “anchoring elements” (AEs), 3–4 base pair sequences, are identified in Arabidopsis WRKY and human PU.1 TFs crucial for binding affinity. Building on the BEESEM method, the study introduces the AEEscape algorithm, which advances the AE concept by creating a precise model of the position‐specific k‐mer binding energy landscape. This method allows for the direct identification of the dominant role of AEs from experimental data. Moreover, when integrated with genomic data, it reveals an energetic funnel around transcription factor binding sites (TFBSs), which is directly correlated with the density of AEs (AED). The findings not only offer a fresh perspective on TF‐TFBS interactions but also highlight the critical role of AED in gene regulation. These insights can pave the way for innovative strategies to manipulate gene expression.https://doi.org/10.1002/advs.202414823anchoring element (AE)anchoring element density (AED)transcription factor and DNA interactiontranscription factor binding site (TFBS)
spellingShingle Hong Chen
Yongping Xu
Hao Ge
Xiao‐Dong Su
DNA–Protein Binding is Dominated by Short Anchoring Elements
Advanced Science
anchoring element (AE)
anchoring element density (AED)
transcription factor and DNA interaction
transcription factor binding site (TFBS)
title DNA–Protein Binding is Dominated by Short Anchoring Elements
title_full DNA–Protein Binding is Dominated by Short Anchoring Elements
title_fullStr DNA–Protein Binding is Dominated by Short Anchoring Elements
title_full_unstemmed DNA–Protein Binding is Dominated by Short Anchoring Elements
title_short DNA–Protein Binding is Dominated by Short Anchoring Elements
title_sort dna protein binding is dominated by short anchoring elements
topic anchoring element (AE)
anchoring element density (AED)
transcription factor and DNA interaction
transcription factor binding site (TFBS)
url https://doi.org/10.1002/advs.202414823
work_keys_str_mv AT hongchen dnaproteinbindingisdominatedbyshortanchoringelements
AT yongpingxu dnaproteinbindingisdominatedbyshortanchoringelements
AT haoge dnaproteinbindingisdominatedbyshortanchoringelements
AT xiaodongsu dnaproteinbindingisdominatedbyshortanchoringelements