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Author

Kaustubh Wagh

Other affiliations: National Institutes of Health
Bio: Kaustubh Wagh is an academic researcher from University of Maryland, College Park. The author has contributed to research in topics: Transcription factor & Chromatin. The author has an hindex of 2, co-authored 6 publications receiving 41 citations. Previous affiliations of Kaustubh Wagh include National Institutes of Health.

Papers
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Journal ArticleDOI
TL;DR: In this article, the authors used single-molecule tracking and machine-learning-based classification to directly measure the nuclear mobility of the glucocorticoid receptor (GR) in live cells.

64 citations

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TL;DR: In this paper, the authors highlight the importance of mechanotransduction as one of the governing principles of cancer progression and emphasize the need to conduct further studies of the molecular mechanisms involved in sensing mechanical cues and coordinating transcriptional responses.

53 citations

Journal ArticleDOI
TL;DR: In this paper, theoretical and experimental evidence for biomolecular condensates as dynamic regulators of transcription has been discussed and functional consequences for transcription factor dynamics and gene expression are discussed.

18 citations

Journal ArticleDOI
TL;DR: These studies define a role for Bcl10 in TCR-dependent actin dynamics, emphasizing that B cl10 has important cytoskeleton-directed functions that are likely independent of its role in transmission of NF-κB -activating signals.

5 citations

Posted ContentDOI
06 Jun 2021-bioRxiv
TL;DR: Using a molecular simulation platform, called MEDYAN, it is discovered that varying the filament treadmilling rate induces a finite size phase transition in actomyosin network structure, which suggests that the actin cortex is a preferred state of low mechanical energy, which is, importantly, only reachable at high treadmilled rates.
Abstract: In most eukaryotic cells, actin filaments assemble into a shell-like actin cortex under the plasma membrane, controlling cellular morphology, mechanics, and signaling. The actin cortex is highly polymorphic, adopting diverse forms such as the ring-like structures found in podosomes, axonal rings, and immune synapses. The biophysical principles that underlie the formation of actin cortices and their structural plasticity remain unknown. Using a molecular simulation platform, called MEDYAN, we discovered that varying the filament treadmilling rate induces a finite size phase transition in actomyosin network structure. We found that actomyosin networks condense into clusters at low treadmilling rates but form ring-like or cortex-like structures at high treadmilling rates. This mechanism is supported by our corroborating experiments on live T cells, which show that disrupting filament treadmilling induces centripetal collapse of pre-existing actin rings and the formation of clusters. Our analyses suggest that the actin cortex is a preferred state of low mechanical energy, which is, importantly, only reachable at high treadmilling rates.

2 citations


Cited by
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Journal ArticleDOI
TL;DR: In this article, the authors proposed a continuum of affinities model to explain transcription factor (TF) dynamics, which is consistent with complex interactions of TFs with multiple nuclear domains as well as binding and searching on the chromatin template.
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.

53 citations

Journal ArticleDOI
TL;DR: In this article , the authors used high-resolution Micro-C and nascent transcript profiling in mouse embryonic stem cells and found that E-P interactions are largely insensitive to acute depletion of CTCF, cohesin or WAPL.
Abstract: It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression of most genes despite substantially perturbing three-dimensional (3D) genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling in mouse embryonic stem cells. We find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-h) depletion of CTCF, cohesin or WAPL. YY1 has been proposed as a structural regulator of E-P loops, but acute YY1 depletion also had minimal effects on E-P loops, transcription and 3D genome folding. Strikingly, live-cell, single-molecule imaging revealed that cohesin depletion reduced transcription factor (TF) binding to chromatin. Thus, although CTCF, cohesin, WAPL or YY1 is not required for the short-term maintenance of most E-P interactions and gene expression, our results suggest that cohesin may facilitate TFs to search for and bind their targets more efficiently.

44 citations

Journal ArticleDOI
TL;DR: In this article , the authors proposed a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and discuss the strategies, techniques and challenges involved.
Abstract: In the past decade, membraneless assemblies known as biomolecular condensates have been reported to play key roles in many cellular functions by compartmentalizing specific proteins and nucleic acids in subcellular environments with distinct properties. Furthermore, growing evidence supports the view that biomolecular condensates often form by phase separation, in which a single-phase system demixes into a two-phase system consisting of a condensed phase and a dilute phase of particular biomolecules. Emerging understanding of condensate function in normal and aberrant cellular states, and of the mechanisms of condensate formation, is providing new insights into human disease and revealing novel therapeutic opportunities. In this Perspective, we propose that such insights could enable a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and we discuss the strategies, techniques and challenges involved.

44 citations

Posted ContentDOI
14 Jul 2021-bioRxiv
TL;DR: In this paper, the authors used high-resolution Micro-C and nascent transcript profiling to find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-hour) depletion of CTCF, cohesin, and WAPL.
Abstract: It remains unclear why acute depletion of CTCF and cohesin only marginally affects expression of most genes despite substantially perturbing 3D genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling to find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-hour) depletion of CTCF, cohesin, and WAPL. YY1 has been proposed to be a structural regulator of E-P loops, but acute YY1 depletion also had minimal effects on E-P loops, transcription, and 3D genome folding. Strikingly, live-cell single-molecule imaging revealed that cohesin depletion reduced transcription factor binding to chromatin. Thus, although neither CTCF, cohesin, WAPL, nor YY1 are required for the short-term maintenance of most E-P interactions and gene expression, we propose that cohesin may serve as a "transcription factor binding platform" that facilitates transcription factor binding to chromatin.

35 citations