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Article
Cell Biology
Karsten Rippe et al.
Summary: This study explores the functional attributes of distinct clusters of RNA polymerase II inside eukaryotic cell nuclei and the mechanisms underlying their formation. It also discusses how the concept of proteins and RNA phase-separating into liquid-like droplets drives the formation of transcriptionally-active subcompartments and how the different ways of assembling the active RNA polymerase II transcriptional machinery relate to nuclear compartmentalization.
CURRENT OPINION IN CELL BIOLOGY
(2022)
Article
Cell Biology
Hiroshi Kimura et al.
Summary: Recent advances in microscopy techniques have revealed the formation of transcription foci by RNA polymerase II (RNAP2) in the nucleus, which depend on its phosphorylation states. Spatially separated initiation and elongation foci have also been observed, suggesting the presence of transcription initiation and elongation factories.
CURRENT OPINION IN CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Musacchio
Summary: Molecular mechanistic biology has delved into the basic building blocks of life, uncovering their interactions and proposing strategies for biological processes. The concept of biomolecular phase separation emphasizes the driving force of interactions, but its validation is challenging. Highly specific interactions may be the main driver of subcellular compartment formation, while phase separation can be locally utilized in specific instances.
Article
Physics, Multidisciplinary
Jose A. Morin et al.
Summary: This study investigates the nature of transcription factor condensates and demonstrates that transcription factors can undergo phase separation at high concentrations and form condensates on DNA at low concentrations. These condensates are shown to form on DNA as a type of surface condensation and are correlated with DNA sequence, thus explaining the size and position control of surface condensates.
Article
Multidisciplinary Sciences
Jessica Zuin et al.
Summary: This study reveals a nonlinear relationship between the contact probabilities of an enhancer with a promoter and its transcriptional effect. Mathematical modeling suggests that this nonlinearity arises from transient enhancer-promoter interactions being translated into slower promoter bursting dynamics. Additionally, the study shows that enhancer strength determines transcription levels and the sensitivity of a promoter to transcriptional insulation mediated by CTCF.
Article
Multidisciplinary Sciences
Michele Gabriele et al.
Summary: This study reveals the rare and dynamic nature of chromatin looping in the Fbn2 TAD, with a looped fraction of approximately 3 to 6.5% and a median loop lifetime of approximately 10 to 30 minutes. The results suggest that functional interactions may be primarily regulated by single CTCF boundaries rather than the fully CTCF-CTCF looped state.
Article
Genetics & Heredity
Pia Mach et al.
Summary: In mammals, interactions between sequences within topologically associating domains occur frequently and transiently, and become more frequent and longer in the presence of convergent CTCF sites. These interactions stabilize highly dynamic chromosome structures and suppress variability in chromosome folding, suggesting that long-range transcriptional regulation relies on transient physical proximity.
Article
Genetics & Heredity
Tsung-Han S. Hsieh et al.
Summary: Short-term maintenance of most gene expression and enhancer-promoter interactions does not require CTCF, Cohesin, WAPL, or YY1, but Cohesin may facilitate transcription factor binding to targets more efficiently.
Article
Multidisciplinary Sciences
Hiroaki Ohishi et al.
Summary: The authors developed a new tool called STREAMING-tag that can reveal the relationship between transcriptional activity and protein clusters, which is useful for quantitatively understanding transcriptional regulation in living cells.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Shawn Irgen-Gioro et al.
Summary: Fixing cells with paraformaldehyde (PFA) can both enhance and diminish the appearance of liquid-liquid phase separation (LLPS) in living cells. PFA fixation can cause artificial droplet-like puncta to appear in cells that do not have detectable puncta in the live condition. The protein localization in fixed cells depends on the dynamics of protein-protein interactions, the overall rate of fixation, and the difference in fixation rates of different proteins.
Article
Developmental Biology
Viraat Y. Goel et al.
Summary: The 3D organization of the genome plays a crucial role in gene regulation, replication, and repair, but it is still not fully understood. Various chromosome conformation capture methods have revealed genome folding at different scales. Understanding the functional role of each layer of genome organization is essential for comprehending cell state, development, and disease.
WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jonathan E. Henninger et al.
Summary: This study discusses the mechanisms of feedback control in regulating biological processes, especially in transcription regulation. Research indicates that RNA in transcription initiation promotes condensate formation, while RNA produced during elongation stimulates condensate dissolution. Therefore, transcriptional regulation involves a feedback mechanism where transcribed RNA both stimulates and arrests the process.
Article
Biochemistry & Molecular Biology
Kaustubh Wagh et al.
Summary: Studies have shown the crucial role of liquid-liquid phase separation in cellular organization and function, regulating the assembly of transcriptional machinery. While advances in microscopy have demonstrated the prevalence of such condensates, a thorough characterization of the physics of phase separation in transcription is still needed.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Nils Schneider et al.
Summary: The study demonstrates that engineered optogenetic synthetic transcription factors, incorporating intrinsically disordered regions, can form droplets at target promoters and increase gene expression up to fivefold. This approach was effective in multiple mammalian cell lines and in mice.
Article
Multidisciplinary Sciences
Yodai Takei et al.
Summary: This study utilized DNA seqFISH+ technology to image 3,660 chromosomal loci in single mouse embryonic stem cells, along with observing 17 chromatin marks and subnuclear structures by sequential immunofluorescence and the expression profile of 70 RNAs. The results suggest that many loci are consistently associated with immunofluorescence marks and form "fixed points" in nuclear organizations in single cells, while highly expressed genes appear to be pre-positioned to active nuclear zones. The research also uncovered distinct mouse ES cell subpopulations with characteristic combinatorial chromatin states.
Article
Multidisciplinary Sciences
Lennart Hilbert et al.
Summary: This study observed the dynamics of euchromatin organization in pluripotent zebrafish cells during transcription initiation, revealing that accumulation of RNA induces the formation of transcriptionally active regions that tend to separate from transcriptionally inactive euchromatin, forming smaller scale microphases.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Bomyi Lim et al.
Summary: Recent studies have shown that active transcription foci contain clusters of transcriptional activators and Pol II, with implications on the regulation of gene activity.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Takeo Narita et al.
Summary: P300/CBP plays a crucial role in activating enhancers and super-enhancers through catalyzing acetylation, promoting transcription of cell-type-specific genes. The acetyltransferase activity is essential for maintaining cell identity and promoting the recruitment of transcription factors.
Article
Genetics & Heredity
Sergio Martin Espinola et al.
Summary: Single-cell analysis using Hi-M in Drosophila development shows that physical proximity between regulatory regions does not necessarily determine transcriptional states. Multi-way analyses reveal the presence of regulatory hubs before topologically associating domains. The study highlights the early establishment of loop interactions and CRM hubs, which are partially regulated by the pioneer transcription factor Zelda and precede transcriptional activation.
Review
Cell Biology
Ivana Jerkovic et al.
Summary: This review discusses various methods for analyzing 3D genome organization, including sequencing, microscopy, and computational approaches, which have significantly advanced our understanding of nuclear architecture and function.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Review
Cell Biology
Marina Feric et al.
Summary: Phase separation is now a known paradigm to explain self-assembly and organization of membraneless bodies in cells, extending to nucleoprotein complexes like DNA-based structures. Recent observations point to molecular interactions forming biomolecular condensates with distinct properties that affect genome organization and function. The resulting phase behavior of genomes through evolution may play a role in regulatory mechanisms and diseases.
TRENDS IN CELL BIOLOGY
(2021)
Review
Cell Biology
Prashant Bhat et al.
Summary: Gene regulation requires coordination of hundreds of regulatory factors at precise genomic and RNA targets. An emerging explanation suggests that DNA, RNA, and proteins organize into 3D compartments in the nucleus to concentrate functionally related molecules, leading to the formation of condensates that partition the nucleus. This compartmentalization can result in non-stoichiometric molecular interactions and behaviors.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Biology
Jordan Yupeng Xiao et al.
Summary: Animal genomes are organized into topologically associated domains (TADs), which contribute to gene regulation by facilitating enhancer-promoter (E-P) contacts within a TAD and preventing these contacts across TAD borders. Existing models fail to explain the hypersensitive response when disruptions occur at TAD boundaries. A futile cycle model of enhancer-mediated regulation is proposed to explain this hypersensitivity through bistability and hysteresis, showing that E-P biochemical specificity may be an illusion and emphasizing the importance of weak TAD boundaries.
Article
Plant Sciences
Simon Alamos et al.
Summary: RNA-labelling technologies were used to image RNA polymerase II activity in single cells of living tobacco and Arabidopsis plants, revealing a switch-like behavior in response to external signals. The results showed that cellular heterogeneity in transcriptional dynamics mainly originates from stochasticity in individual alleles, enabling quantitative studies of transcriptional programs in single plant cells.
Article
Plant Sciences
Sahar Hani et al.
Summary: In this study, real-time visualization of transcriptional regulation in living Arabidopsis plants was achieved using the latest-generation RNA imaging system combined with microfluidics. The research revealed quantitative measurements of transcriptional activity at single loci in single cells, gene bursting, and large allelic differences, as well as the dominance of intrinsic noise in transcriptional control. Additionally, fast kinetics of transcriptional repression triggered by phosphate in roots and heterogeneity between neighboring cells were observed, providing valuable insights for future studies of signaling processes in plants.
Review
Biochemistry & Molecular Biology
Joseph Rodriguez et al.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 89
(2020)
Article
Multidisciplinary Sciences
Hiroshi Ochiai et al.
Article
Biochemistry & Molecular Biology
Jun-Han Su et al.
Article
Biochemistry & Molecular Biology
Jieru Li et al.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2020)
Article
Biology
Jeffrey M. Alexander et al.
Article
Biochemistry & Molecular Biology
Jieru Li et al.
Article
Biochemistry & Molecular Biology
Rui Xiao et al.
Review
Biochemistry & Molecular Biology
Michael I. Robson et al.
Article
Biochemistry & Molecular Biology
Nezha S. Benabdallah et al.
Article
Cell Biology
David T. McSwiggen et al.
GENES & DEVELOPMENT
(2019)
Review
Biophysics
Fabian Erdel et al.
BIOPHYSICAL JOURNAL
(2018)
Article
Multidisciplinary Sciences
Benjamin R. Sabari et al.
Article
Multidisciplinary Sciences
Won-Ki Cho et al.
Article
Multidisciplinary Sciences
Mahipal Ganji et al.
Article
Genetics & Heredity
Hongtao Chen et al.
Article
Multidisciplinary Sciences
Bogdan Bintu et al.
Article
Biology
Mustafa Mir et al.
Review
Multidisciplinary Sciences
Eileen E. M. Furlong et al.
Article
Cell Biology
Mustafa Mir et al.
GENES & DEVELOPMENT
(2017)
Article
Biochemistry & Molecular Biology
Abraham S. Weintraub et al.
Review
Biochemistry & Molecular Biology
Denes Hnisz et al.
Article
Cell Biology
Geoffrey Fudenberg et al.
Article
Cell Biology
Francois Le Dily et al.
GENES & DEVELOPMENT
(2014)
Article
Multidisciplinary Sciences
Ibrahim I. Cisse et al.
Review
Biochemistry & Molecular Biology
Stephanie C. Weber et al.
Article
Biochemistry & Molecular Biology
Jiangang Liu et al.
