scholarly journals Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a key organizer of higher-order chromatin architecture

2018 ◽  
Vol 293 (10) ◽  
pp. 3607-3624 ◽  
Author(s):  
Kenji Moriyama ◽  
Naoko Yoshizawa-Sugata ◽  
Hisao Masai
Keyword(s):  
Protein A ◽  
Higher Order ◽  
Oligomer Formation ◽  
Chromatin Architecture ◽  
G Quadruplex

scholarly journals Stabilization of a G-Quadruplex from Unfolding by Replication Protein A Using Potassium and the Porphyrin TMPyP4

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Aishwarya Prakash ◽  
Fabien Kieken ◽  
Luis A. Marky ◽  
Gloria E. O. Borgstahl
Keyword(s):  
Dna Replication ◽  
Protein A ◽  
Thermal Stabilization ◽  
Replication Protein A ◽  
Replication Protein ◽  
Unique Problem ◽  
Ssdna Binding ◽  
Binding Domains ◽  
G Quadruplex ◽  
Stabilization Effect

Replication protein A (RPA) plays an essential role in DNA replication by binding and unfolding non-canonical single-stranded DNA (ssDNA) structures. Of the six RPA ssDNA binding domains (labeled A-F), RPA-CDE selectively binds a G-quadruplex forming sequence (5′-TAGGGGAAGGGTTGGAGTGGGTT-3′called Gq23). In K+, Gq23 forms a mixed parallel/antiparallel conformation, and in Na+Gq23 has a less stable (TMlowered by ∼20∘C), antiparallel conformation. Gq23 is intramolecular and 1D NMR confirms a stable G-quadruplex structure in K+. Full-length RPA and RPA-CDE-core can bind and unfold the Na+form of Gq23 very efficiently, but complete unfolding is not observed with the K+form. Studies with G-quadruplex ligands, indicate that TMPyP4 has a thermal stabilization effect on Gq23 in K+, and inhibits complete unfolding by RPA and RPA-CDE-core. Overall these data indicate that G-quadruplexes present a unique problem for RPA to unfold and ligands, such as TMPyP4, could possibly hinder DNA replication by blocking unfolding by RPA.

Targeting Higher-Order DNA: Beyond the G-Quadruplex

ChemBioChem ◽  
2009 ◽  
Vol 10 (13) ◽  
pp. 2139-2143 ◽  
Author(s):  
Lesley A. Howell ◽  
Mark Searcey
Keyword(s):  
Higher Order ◽  
G Quadruplex

scholarly journals Three-dimensional localization of CENP-A suggests a complex higher order structure of centromeric chromatin

2008 ◽  
Vol 183 (7) ◽  
pp. 1193-1202 ◽  
Author(s):  
Owen J. Marshall ◽  
Alan T. Marshall ◽  
K.H. Andy Choo
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Protein A ◽  
Three Dimensional ◽  
Higher Order ◽  
Order Structure ◽  
Mitotic Chromosomes ◽  
Centromeric Chromatin ◽  
Centromere Protein A ◽  
Transmission Electron ◽  
Histone H3 Variant

The histone H3 variant centromere protein A (CENP-A) is central to centromere formation throughout eukaryotes. A long-standing question in centromere biology has been the organization of CENP-A at the centromere and its implications for the structure of centromeric chromatin. In this study, we describe the three-dimensional localization of CENP-A at the inner kinetochore plate through serial-section transmission electron microscopy of human mitotic chromosomes. At the kinetochores of normal centromeres and at a neocentromere, CENP-A occupies a compact domain at the inner kinetochore plate, stretching across two thirds of the length of the constriction but encompassing only one third of the constriction width and height. Within this domain, evidence of substructure is apparent. Combined with previous chromatin immunoprecipitation results (Saffery, R., H. Sumer, S. Hassan, L.H. Wong, J.M. Craig, K. Todokoro, M. Anderson, A. Stafford, and K.H.A. Choo. 2003. Mol. Cell. 12:509–516; Chueh, A.C., L.H. Wong, N. Wong, and K.H.A. Choo. 2005. Hum. Mol. Genet. 14:85–93), our data suggest that centromeric chromatin is arranged in a coiled 30-nm fiber that is itself coiled or folded to form a higher order structure.

scholarly journals Higher order chromatin architecture in the cell nucleus: on the way from structure to function

2004 ◽  
Vol 96 (8) ◽  
pp. 555-567 ◽  
Author(s):  
Thomas Cremer ◽  
Katrin Küpper ◽  
Steffen Dietzel ◽  
Stanislav Fakan
Keyword(s):  
Cell Nucleus ◽  
Higher Order ◽  
Chromatin Architecture ◽  
The Way

scholarly journals 3D Chromatin Remodeling Potentiates Transcriptional Programs Driving Cell Invasion

2021 ◽  
Author(s):  
Benjamin Lebeau ◽  
Maika Jangal ◽  
Tiejun Zhao ◽  
Cheng Kit Wong ◽  
Nolan Wong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cell Invasion ◽  
De Novo ◽  
Higher Order ◽  
Transcriptional Networks ◽  
Copy Number Loss ◽  
Breast Cancers ◽  
Chromatin Architecture ◽  
Oncogenic Pathways ◽  
The Impact

Abstract The contribution of deregulated chromatin architecture, including topologically associated domains (TADS), to cancer progression remains ambiguous. CTCF is a central regulator of higher-order chromatin structure that undergoes copy number loss in over half of all breast cancers, but the impact of this defect on epigenetic programming and chromatin architecture remains unclear. We find that under physiological conditions, CTCF organizes sub-TADs to limit the expression of oncogenic pathways, including PI3K and cell adhesion networks. Loss of a single CTCF allele potentiates cell invasion through compromised chromatin insulation and a reorganization of chromatin architecture and histone programming that facilitates de novo promoter-enhancer contacts. However, this change in the higher-order chromatin landscape leads to a vulnerability to inhibitors of mTOR. These data support a model whereby sub-TAD reorganization drives both the modification of histones at de novo enhancer promoter-contacts and transcriptional upregulation of oncogenic transcriptional networks.

scholarly journals Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

2020 ◽  
Author(s):  
Lei Chang ◽  
Mengfan Li ◽  
Shipeng Shao ◽  
Chen Li ◽  
Shanshan Ai ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Three Dimensional ◽  
Higher Order ◽  
Order Structure ◽  
Chromatin Dynamics ◽  
Lamin B1 ◽  
Chromatin Architecture ◽  
Chromatin Interactions ◽  
Molecular Machinery

Abstract The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.

scholarly journals Aptamers Against the β-Conglutin Allergen: Insights into the Behavior of the Shortest Multimeric(Intra)Molecular DNA G-Quadruplex

2021 ◽  
Vol 22 (3) ◽  
pp. 1150
Author(s):  
Ciara K. O’ Sullivan ◽  
Teresa Mairal ◽  
Miriam Jauset-Rubio ◽  
Marketa Svobodova ◽  
Vasso Skouridou ◽  
...  
Keyword(s):  
High Performance ◽  
Polyacrylamide Gel Electrophoresis ◽  
Time Of Flight ◽  
Higher Order ◽  
Binding Ability ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
G Quadruplex ◽  
Derivatives Of ◽  
Order Structures

In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5′ or 3′ end or at both ends. The TT-tail at the 5′ end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed.

scholarly journals Chromatin-lamin B1 interaction promotes genomic compartmentalization and constrains chromatin dynamics

2019 ◽  
Author(s):  
Lei Chang ◽  
Mengfan Li ◽  
Shipeng Shao ◽  
Boxin Xue ◽  
Yingping Hou ◽  
...  
Keyword(s):  
Higher Order ◽  
Order Structure ◽  
Chromatin Dynamics ◽  
Lamin B1 ◽  
Structure And Dynamics ◽  
Chromatin Architecture ◽  
Topologically Associating Domains ◽  
Chromosomal Territory ◽  
Molecular Machinery

AbstractThe eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized chromatin architecture and dynamics remains poorly understood. Here by combining imaging and Hi-C sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to chromatin redistribution and decompaction. Consequently, the inter-chromosomal interactions and overlap between chromosome territories are increased. Moreover, Hi-C data revealed that lamin B1 is required for the integrity and segregation of chromatin compartments but not for the topologically associating domains (TADs). We further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nuclear interior. Taken together, our data suggest that chromatin-lamin B1 interactions promote chromosomal territory segregation and genomic compartmentalization, and confine chromatin dynamics, supporting its crucial role in chromatin higher-order structure and dynamics.

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