scholarly journals Probing Transcription Factor Dynamics at the Single-Molecule Level in a Living Cell

Science ◽  
2007 ◽  
Vol 316 (5828) ◽  
pp. 1191-1194 ◽  
Author(s):  
J. Elf ◽  
G.-W. Li ◽  
X. S. Xie
Keyword(s):  
Transcription Factor ◽  
Single Molecule ◽  
Living Cell ◽  
Single Molecule Level

scholarly journals Power-law behavior of transcription factor dynamics at the single-molecule level implies a continuum affinity model

2021 ◽  
Author(s):  
David A Garcia ◽  
Gregory Fettweis ◽  
Diego M Presman ◽  
Ville Paakinaho ◽  
Christopher Jarzynski ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Single Molecule ◽  
Power Law ◽  
Dwell Time ◽  
Specific Binding ◽  
Power Law Distribution ◽  
Single Molecule Level ◽  
Binding Behavior ◽  
Chromatin Template ◽  
Nuclear Domains

Abstract Single-molecule tracking (SMT) allows the study of transcription factor (TF) dynamics in the nucleus, giving important information regarding the diffusion and binding behavior of these proteins in the nuclear environment. Dwell time distributions obtained by SMT for most TFs appear to follow bi-exponential behavior. This has been ascribed to two discrete populations of TFs—one non-specifically bound to chromatin and another specifically bound to target sites, as implied by decades of biochemical studies. However, emerging studies suggest alternate models for dwell-time distributions, indicating the existence of more than two populations of TFs (multi-exponential distribution), or even the absence of discrete states altogether (power-law distribution). Here, we present an analytical pipeline to evaluate which model best explains SMT data. We find that a broad spectrum of TFs (including glucocorticoid receptor, oestrogen receptor, FOXA1, CTCF) follow a power-law distribution of dwell-times, blurring the temporal line between non-specific and specific binding, suggesting that productive binding may involve longer binding events than previously believed. From these observations, we propose a continuum of affinities model to explain TF dynamics, that is consistent with complex interactions of TFs with multiple nuclear domains as well as binding and searching on the chromatin template.

scholarly journals Transcription Factor Target Search Strategy at the Single Molecule Level in Eukaryotic Cells

2012 ◽  
Vol 102 (3) ◽  
pp. 288a
Author(s):  
Lydia Boudarene ◽  
Vincent Récamier ◽  
Davide Normanno ◽  
Ignacio Izzedine ◽  
Ibrahim Cissé ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Single Molecule ◽  
Search Strategy ◽  
Eukaryotic Cells ◽  
Target Search ◽  
Single Molecule Level ◽  
Transcription Factor Target

scholarly journals Quantifying transcription factor binding dynamics at the single-molecule level in live cells

Methods ◽  
2017 ◽  
Vol 123 ◽  
pp. 76-88 ◽  
Author(s):  
Diego M. Presman ◽  
David A. Ball ◽  
Ville Paakinaho ◽  
Jonathan B. Grimm ◽  
Luke D. Lavis ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Single Molecule ◽  
Transcription Factor Binding ◽  
Live Cells ◽  
Single Molecule Level ◽  
Factor Binding

scholarly journals Power-law behaviour of transcription factor dynamics at the single-molecule level implies a continuum affinity model

2019 ◽  
Author(s):  
David A. Garcia ◽  
Gregory Fettweis ◽  
Diego M. Presman ◽  
Ville Paakinaho ◽  
Christopher Jarzynski ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Single Molecule ◽  
Power Law ◽  
Specific Binding ◽  
Power Law Distribution ◽  
Single Molecule Level ◽  
Complex Interactions ◽  
Chromatin Template ◽  
Nuclear Domains

ABSTRACTSingle-molecule tracking (SMT) allows the study of transcription factor (TF) dynamics in the nucleus, giving important information regarding the search and binding behaviour of these proteins in the nuclear environment. Dwell time distributions for most TFs have been described by SMT to follow bi-exponential behaviour. This is consistent with the existence of two discrete populations bound to chromatin in vivo, one non-specifically bound to chromatin (i.e. searching mode) and another specifically bound to target sites, as originally defined by decades of biochemical studies. However, alternative models have started to emerge, from multiple exponential components to power-law distributions. Here, we present an analytical pipeline with an unbiased model selection approach based on different statistical metrics to determine the model that best explains SMT data. We found that a broad spectrum of TFs (including glucocorticoid receptor, oestrogen receptor, FOXA1, CTCF) follow a power-law distribution, blurring the temporal line between non-specific and specific binding, and suggesting that productive binding may involve longer binding events than previously thought. We propose a continuum of affinities model to explain the experimental data, consistent with the movement of TFs through complex interactions with multiple nuclear domains as well as binding and searching on the chromatin template.

scholarly journals Quantitative Transcription Factor Binding Kinetics at the Single-Molecule Level

2009 ◽  
Vol 96 (2) ◽  
pp. 609-620 ◽  
Author(s):  
Yufang Wang ◽  
Ling Guo ◽  
Ido Golding ◽  
Edward C. Cox ◽  
N.P. Ong
Keyword(s):  
Transcription Factor ◽  
Single Molecule ◽  
Transcription Factor Binding ◽  
Binding Kinetics ◽  
Single Molecule Level ◽  
Factor Binding

Modern biophysical approaches probe transcription-factor-induced DNA bending and looping

2013 ◽  
Vol 41 (1) ◽  
pp. 368-373 ◽  
Author(s):  
Andreas Gietl ◽  
Dina Grohmann
Keyword(s):  
Transcription Factor ◽  
Single Molecule ◽  
Conformational Changes ◽  
Double Helix ◽  
Dna Bending ◽  
Living Organism ◽  
Single Molecule Level ◽  
Specific Manner ◽  
Biophysical Techniques ◽  
Promoter Dna

The genetic information of every living organism is stored in its genomic DNA that is perceived as a chemically stable and robust macromolecule. But at the same time, to fulfil its functions properly, it also needs to be highly dynamic and flexible. This includes partial melting of the double helix or compaction and bending of the DNA often brought about by protein factors that are able to interact with DNA stretches in a specific and non-specific manner. The conformational changes in the DNA need to be understood in order to describe biological systems in detail. As these events play out on the nanometre scale, new biophysical approaches have been employed to monitor conformational changes in this regime at the single-molecule level. Focusing on transcription factor action on promoter DNA, we discuss how current biophysical techniques are able to quantitatively describe this molecular process.

Atomic Force Microscopy (AFM) for Topography and Recognition Imaging at Single Molecule Level

2013 ◽  
pp. 102-112
Author(s):  
Memed Duman ◽  
Andreas Ebner ◽  
Christian Rankl ◽  
Jilin Tang ◽  
Lilia A. Chtcheglova ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Single Molecule ◽  
Single Molecule Level ◽  
Force Microscopy ◽  
Atomic Force ◽  
Recognition Imaging
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