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Nucleosome Spacing Can Fine-Tune Higher Order Chromatin Assembly.
bioRxiv
December 2024
Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cellular chromatin displays heterogeneous structure and dynamics, properties that control diverse nuclear processes. Models invoke phase separation of conformational ensembles of chromatin fibers as a mechanism regulating chromatin organization . Here we combine biochemistry and molecular dynamics simulations to examine, at single base-pair resolution, how nucleosome spacing controls chromatin phase separation.
View Article and Find Full Text PDFThe triple code model for advancing research in rare and undiagnosed diseases beyond the base pairs.
Epigenomics
December 2024
Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Rare and undiagnosed diseases pose significant challenges for understanding their mechanisms, diagnosis, and treatment. The Triple Code Model, an integrative paradigm described here, considers the combined influence of the genetic code, epigenetic code, and nuclear structure (an emerging code), as fundamental biochemical mechanisms underlying many rare diseases. Studies demonstrate dysfunctional membrane and cytoplasmic signals instruct the epigenome to ultimately impact the 3D structure and dynamics of the nucleus, highlighting their close interrelationships.
View Article and Find Full Text PDFOptogenetic Control of Phosphate-Responsive Genes Using Single-Component Fusion Proteins in .
ACS Synth Biol
December 2024
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, New York 10031, United States.
Article Synopsis
- Blue light can activate light-sensitive proteins, like VP-EL222, enabling new optogenetic tools to control cellular functions in yeast.
- We tested the VP-EL222 protein's ability to adjust gene expression based on light intensity and duration, finding it can accommodate larger functional components.
- Our research shows how to both activate and repress gene expression using EL222, and how this system can work alongside natural phosphate-regulated controls, enhancing its use in various biological studies.
Transcription-dependent mobility of single genes and genome-wide motions in live human cells.
Nat Commun
October 2024
Center for Soft Matter Research, Department of Physics, New York University, New York, NY, 10003, USA.
Article Synopsis
- The human genome is constantly changing at both the gene and genome levels, with chromatin being remodeled during key processes like transcription and DNA repair.
- Researchers explored the relationship between genetic activity and the movement of nearby genomic regions, finding that gene transcription can influence larger genomic motions in less dense chromatin areas.
- The study highlights how gene activity and chromatin density interact to affect the overall organization of the genome, which is crucial for understanding gene regulation and expression.
Inter3D: Capture of TAD Reorganization Endows Variant Patterns of Gene Transcription.
Genomics Proteomics Bioinformatics
September 2024
State Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Research Center for Stem Cells, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
Article Synopsis
- * The study introduced a new method called Inter3D to identify genes affected by these TAD changes, demonstrating that TAD segregation can disrupt looping structures related to the MYL12B gene, leading to reduced gene expression.
- * Conversely, the fusion of TADs can enhance interactions that may activate the CYP27B1 gene, highlighting the complex role of TAD reorganization in gene transcription and providing a valuable tool for further research.
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