scholarly journals The needle and the haystack: single molecule tracking to probe the transcription factor search in eukaryotes

2021 ◽  
Author(s):  
Matteo Mazzocca ◽  
Tom Fillot ◽  
Alessia Loffreda ◽  
Daniela Gnani ◽  
Davide Mazza
Keyword(s):  
Single Molecule ◽  
Target Genes ◽  
Eukaryotic Cell ◽  
Search Process ◽  
Single Molecule Tracking ◽  
Search Mechanism ◽  
Complex Organization ◽  
Future Challenges ◽  
Nuclear Environment ◽  
Shed Light

Transcription factors (TFs) regulate transcription of their target genes by identifying and binding to regulatory regions of the genome among billions of potential non-specific decoy sites, a task that is often presented as a ‘needle in the haystack’ challenge. The TF search process is now well understood in bacteria, but its characterization in eukaryotes needs to account for the complex organization of the nuclear environment. Here we review how live-cell single molecule tracking is starting to shed light on the TF search mechanism in the eukaryotic cell and we outline the future challenges to tackle in order to understand how nuclear organization modulates the TF search process in physiological and pathological conditions.

scholarly journals Guided nuclear exploration increases CTCF target search efficiency

2018 ◽  
Author(s):  
Anders S. Hansen ◽  
Assaf Amitai ◽  
Claudia Cattoglio ◽  
Robert Tjian ◽  
Xavier Darzacq
Keyword(s):  
Dna Binding ◽  
Single Molecule ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Target Search ◽  
Single Molecule Tracking ◽  
Search Mechanism ◽  
Binding Factor ◽  
Target Sites ◽  
Mammalian Genomes

Mammalian genomes are enormous. For a DNA-binding protein, this means that the number of non-specific, off-target sites vastly exceeds the number of specific, cognate sites. How mammalian DNA-binding proteins overcome this challenge to efficiently locate their target sites is not known. Here through live-cell single-molecule tracking, we show that CCCTC-binding factor, CTCF, is repeatedly trapped in small zones in the nucleus in a manner that is largely dependent on its RNA-binding region (RBR). Integrating theory, we devise a new model, Anisotropic Diffusion through transient Trapping in Zones (ADTZ), to explain this. Functionally, transient RBR-mediated trapping increases the efficiency of CTCF target search by ∼2.5 fold. Since the RBR-domain also mediates CTCF clustering, our results suggest a “guided” mechanism where CTCF clusters concentrate diffusing CTCF proteins near cognate binding sites, thus increasing the local ON-rate. We suggest that local “guiding” may represent a general target search mechanism in mammalian cells.

Single-molecule tracking in eukaryotic cell nuclei

2006 ◽  
Vol 387 (1) ◽  
pp. 41-44 ◽  
Author(s):  
Jan Peter Siebrasse ◽  
David Grünwald ◽  
Ulrich Kubitscheck
Keyword(s):  
Single Molecule ◽  
Eukaryotic Cell ◽  
Cell Nuclei ◽  
Single Molecule Tracking

Polarization-resolved single-molecule tracking reveal strange dynamics of individual fluorescent tracers through a deep rubbery polymer network

2021 ◽  
Author(s):  
Jaladhar Mahato ◽  
Sukanya Bhattacharya ◽  
Dharmendar Kumar Sharma ◽  
Arindam Chowdhury
Keyword(s):  
Single Molecule ◽  
Local Structure ◽  
Biological Systems ◽  
Polymer Network ◽  
Soft Materials ◽  
Complex Environments ◽  
Fluorescent Tracers ◽  
Single Molecule Tracking ◽  
Structure And Dynamics

Tracking the movement of fluorescent single-molecule (SM) tracers has provided several new insights on the local structure and dynamics in complex environments such as soft materials and biological systems. However,...

scholarly journals Mechanical single-molecule potentiometers with large switching factors from ortho-pentaphenylene foldamers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinshi Li ◽  
Pingchuan Shen ◽  
Shijie Zhen ◽  
Chun Tang ◽  
Yiling Ye ◽  
...  
Keyword(s):  
Charge Transport ◽  
Single Molecule ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Helical Structures ◽  
Anchoring Groups ◽  
Molecular Conductance ◽  
And Control ◽  
Helical Molecules ◽  
Shed Light

AbstractMolecular potentiometers that can indicate displacement-conductance relationship, and predict and control molecular conductance are of significant importance but rarely developed. Herein, single-molecule potentiometers are designed based on ortho-pentaphenylene. The ortho-pentaphenylene derivatives with anchoring groups adopt multiple folded conformers and undergo conformational interconversion in solutions. Solvent-sensitive multiple conductance originating from different conformers is recorded by scanning tunneling microscopy break junction technique. These pseudo-elastic folded molecules can be stretched and compressed by mechanical force along with a variable conductance by up to two orders of magnitude, providing an impressively higher switching factor (114) than the reported values (ca. 1~25). The multichannel conductance governed by through-space and through-bond conducting pathways is rationalized as the charge transport mechanism for the folded ortho-pentaphenylene derivatives. These findings shed light on exploring robust single-molecule potentiometers based on helical structures, and are conducive to fundamental understanding of charge transport in higher-order helical molecules.

scholarly journals Phase-Separated Transcriptional Condensates Accelerate Target-Search Process Revealed by Live-Cell Single-Molecule Imaging

Cell Reports ◽  
2020 ◽  
Vol 33 (2) ◽  
pp. 108248 ◽  
Author(s):  
Samantha Kent ◽  
Kyle Brown ◽  
Chou-hsun Yang ◽  
Njood Alsaihati ◽  
Christina Tian ◽  
...  
Keyword(s):  
Single Molecule ◽  
Live Cell ◽  
Search Process ◽  
Single Molecule Imaging ◽  
Target Search

scholarly journals Epigenetic Methylations on N6-Adenine and N6-Adenosine with the same Input but Different Output

2019 ◽  
Vol 20 (12) ◽  
pp. 2931 ◽  
Author(s):  
Zhiqing Li ◽  
Ping Zhao ◽  
Qingyou Xia
Keyword(s):  
Genetic Information ◽  
Target Genes ◽  
Technological Development ◽  
Wide Spectrum ◽  
Functional Identification ◽  
Methyl Group ◽  
Cellular Processes ◽  
Dna And Rna ◽  
Future Challenges ◽  
Detection Strategies

Epigenetic modifications on individual bases in DNA and RNA can encode inheritable genetic information beyond the canonical bases. Among the nucleic acid modifications, DNA N6-methadenine (6mA) and RNA N6-methyladenosine (m6A) have recently been well-studied due to the technological development of detection strategies and the functional identification of modification enzymes. The current findings demonstrate a wide spectrum of 6mA and m6A distributions from prokaryotes to eukaryotes and critical roles in multiple cellular processes. It is interesting that the processes of modification in which the methyl group is added to adenine and adenosine are the same, but the outcomes of these modifications in terms of their physiological impacts in organisms are quite different. In this review, we summarize the latest progress in the study of enzymes involved in the 6mA and m6A methylation machinery, including methyltransferases and demethylases, and their functions in various biological pathways. In particular, we focus on the mechanisms by which 6mA and m6A regulate the expression of target genes, and we highlight the future challenges in epigenetic regulation.

scholarly journals Synthesis and Photostability of Unimolecular Submersible Nanomachines: Toward Single-Molecule Tracking in Solution

2016 ◽  
Vol 18 (10) ◽  
pp. 2343-2346 ◽  
Author(s):  
Víctor García-López ◽  
Jonathan Jeffet ◽  
Shunsuke Kuwahara ◽  
Angel A. Martí ◽  
Yuval Ebenstein ◽  
...  
Keyword(s):  
Single Molecule ◽  
Single Molecule Tracking
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