scholarly journals Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element

2014 ◽  
Vol 212 (1) ◽  
pp. 107-120 ◽  
Author(s):  
Kinjal Majumder ◽  
Olivia I. Koues ◽  
Elizabeth A.W. Chan ◽  
Katherine E. Kyle ◽  
Julie E. Horowitz ◽  
...  

Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containing element, directly tethers distal portions of the Vβ array to the RC. The second element is a chromatin barrier that protects the tether from hyperactive RC chromatin. When the second element is removed, active RC chromatin spreads upstream, forcing the tether to serve as a new barrier. Acquisition of barrier function by the CTCF element disrupts contacts between distal Vβ gene segments and significantly alters Tcrb repertoires. Our findings reveal a separation of function for RC-flanking regions, in which anchors for long-range recombination must be cordoned off from hyperactive RC landscapes by chromatin barriers.

2008 ◽  
Vol 205 (4) ◽  
pp. 747-750 ◽  
Author(s):  
Adam Williams ◽  
Richard A. Flavell

The spatial organization of the genome is thought to play an important part in the coordination of gene regulation. New techniques have been used to identify specific long-range interactions between distal DNA sequences, revealing an ever-increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a versatile zinc finger protein with diverse regulatory functions. New data now help define how CTCF mediates both long-range intrachromosomal and interchromosomal interactions, and highlight CTCF as an important factor in determining the three-dimensional structure of the genome.


2017 ◽  
Author(s):  
Jongjoo Lee ◽  
Ivan Krivega ◽  
Ryan K. Dale ◽  
Ann Dean

SUMMARYLineage-specific transcription factors are critical for long-range enhancer interactions but direct or indirect contributions of architectural proteins such as CTCF to enhancer function remain less clear. The LDB1 complex mediates enhancer-gene interactions at the β-globin locus through LDB1 self-interaction. We find that a novel LDB1-bound enhancer upstream of carbonic anhydrase 2 (Car2) activates its expression by interacting directly with CTCF at the gene promoter. Both LDB1 and CTCF are required for enhancer-Car2 looping and the domain of LDB1 contacted by CTCF is necessary to rescue Car2 transcription in LDB1 deficient cells. Genome wide studies and CRISPR/Cas9 genome editing indicate that LDB1-CTCF enhancer looping underlies activation of a substantial fraction of erythroid genes. Our results provide a mechanism by which long-range interactions of architectural protein CTCF can be tailored to achieve a tissue-restricted pattern of chromatin loops and gene expression.


2017 ◽  
Vol 21 (6) ◽  
pp. 161-170
Author(s):  
A.A. Biryukov ◽  
Y.V. Degtyarova

The article deals with two-dimensional and three-dimensional Ising models with the long-range spin interactions. The intensity of interaction between the spins relies decreasing with distance r as a power law r-d-σ with dimensional d and parameter σ. The research are conducted by Monte-Carlo method with Metropolis algorithm using parallel computing techniques. On the basis of nu- merical simulation the dependence of the phase transition temperature on the parameter σ is found. It is shown that at phase transition temperature decreases with increasing σ.


1995 ◽  
Vol 283 ◽  
pp. 43-95 ◽  
Author(s):  
P. K. Yeung ◽  
James G. Brasseur ◽  
Qunzhen Wang

As discussed in a recent paper by Brasseur & Wei (1994), scale interactions in fully developed turbulence are of two basic types in the Fourier-spectral view. The cascade of energy from large to small scales is embedded within ‘local-to-non-local’ triadic interactions separated in scale by a decade or less. ‘Distant’ triadic interactions between widely disparate scales transfer negligible energy between the largest and smallest scales, but directly modify the structure of the smallest scales in relationship to the structure of the energy-dominated large scales. Whereas cascading interactions tend to isotropize the small scales as energy moves through spectral shells from low to high wavenumbers, distant interactions redistribute energy within spectral shells in a manner that leads to anisotropic redistributions of small-scale energy and phase in response to anisotropic structure in the large scales. To study the role of long-range interactions in small-scale dynamics, Yeung & Brasseur (1991) carried out a numerical experiment in which the marginally distant triads were purposely stimulated through a coherent narrow-band anisotropic forcing at the large scales readily interpretable in both the Fourier- and physical-space views. It was found that, after one eddy turnover time, the smallest scales rapidly became anisotropic as a direct consequence of the marginally distant triadic group in a manner consistent with the distant triadic equations. Because these asymptotic equations apply in the infinite Reynolds number limit, Yeung & Brasseur argued that the observed long-range effects should be applicable also at high Reynolds numbers.We continue the analysis of forced simulations in this study, focusing (i) on the detailed three-dimensional restructuring of the small scales as predicted by the asymptotic triadic equations, and (ii) on the relationship between Fourier- and physical-space evolution during forcing. We show that the three-dimensional restructuring of small-scale energy and vorticity in Fourier space from large-scale forcing is predicted in some detail by the distant triadic equations. We find that during forcing the distant interactions alter small-scale structure in two ways: energy is redistributed anisotropically within high-wavenumber spectral shells, and phase correlations are established at the small scales by the distant interactions. In the numerical experiments, the long-range interactions create two pairs of localized volumes of concentrated energy in three-dimensional Fourier space at high wavenumbers in which the Fourier modes are phase coupled. Each pair of locally phase-correlated volumes of Fourier modes separately corresponds to aligned vortex tubes in physical space in two orthogonal directions. We show that the dynamics of distant interactions in creating small-scale anisotropy may be described in physical space by differential advection and distortion of small-scale vorticity by the coherent large-scale energy-containing eddies, producing anisotropic alignment of small-scale vortex tubes.Scaling arguments indicate a disparity in timescale between distant triadic interactions and energy-cascading local-to-non-local interactions which increases with scale separation. Consequently, the small scales respond to forcing initially through the distant interactions. However, as energy cascades from the large-scale to the small-scale Fourier modes, the stimulated distant interactions become embedded within a sea of local-to-non-local energy cascading interactions which reduce (but do not eliminate) small-scale anisotropy at later times. We find that whereas the small-scale structure is still anisotropic at these later times, the second-order velocity moment tensor is insensitive to this anisotropy. Third-order moments, on the other hand, do detect the anisotropy. We conclude that whereas a single statistical measure of anisotropy can be used to indicate the presence of anisotropy, a null result in that measure does not necessarily imply that the signal is isotropic. The results indicate that non-equilibrium non-stationary turbulence is particularly sensitive to long-range interactions and deviations from local isotropy.


Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1308
Author(s):  
Arvind Ramanathan ◽  
Akash Parvatikar ◽  
Srinivas C. Chennubhotla ◽  
Yang Mei ◽  
Sangita C. Sinha

Viral BCL2 proteins (vBCL2s) help to sustain chronic infection of host proteins to inhibit apoptosis and autophagy. However, details of conformational changes in vBCL2s that enable binding to BH3Ds remain unknown. Using all-atom, multiple microsecond-long molecular dynamic simulations (totaling 17 μs) of the murine γ-herpesvirus 68 vBCL2 (M11), and statistical inference techniques, we show that regions of M11 transiently unfold and refold upon binding of the BH3D. Further, we show that this partial unfolding/refolding within M11 is mediated by a network of hydrophobic interactions, which includes residues that are 10 Å away from the BH3D binding cleft. We experimentally validate the role of these hydrophobic interactions by quantifying the impact of mutating these residues on binding to the Beclin1/BECN1 BH3D, demonstrating that these mutations adversely affect both protein stability and binding. To our knowledge, this is the first study detailing the binding-associated conformational changes and presence of long-range interactions within vBCL2s.


2021 ◽  
Author(s):  
Bingbing Li ◽  
Dan Lin ◽  
Xiaoqiao Zhai ◽  
Guoqiang Fan ◽  
Zhenli Zhao ◽  
...  

Abstract Higher-order chromatin structures play important roles in regulating multiple biological processes, growth and development, biotic and abiotic stress response. However, little is known about three-dimensional chromatin structures in Paulownia, or about whole-genome chromatin conformational changes that occur in response to Paulownia witches’ broom (PaWB) disease. We used high-throughput chromosome conformation capture (Hi-C) to obtain genome-wide profiles of chromatin conformation in healthy and phytoplasma-infected Paulownia fortunei genome. The heatmap results indicated that the strongest interactions between chromosomes were in the telomeres. We confirmed the main structural characteristics, such as A/B compartments, topologically associated domains, and chromatin loops were prominent in Paulownia genome and clearly altered in phytoplasma-infected plants. By combining chromatin Immunoprecipitation sequencing, Hi-C signals, and RNA sequencing data, we inferred that the chromatin structure changed and the modification levels of three histones (H3K4me3/K9ac/K36me3) increased in phytoplasma-infected P. fortunei, which was associated with changes of transcriptional activity. We concluded that epigenetic modifications, transcriptional activity might function in combination to shape chromatin packing in healthy and phytoplasm-infected Paulownia. Finally, 11 genes (such as RPN6, Sec61 subunit alpha), commonly located at specific TAD boundaries, A/B compartment switching, specific loops, and associated with histone marks, were identified and considered as closely related to PaWB stress. Our results provide new insights into the nexus between gene regulation and chromatin conformational alterations in non-model plants upon phytopathogen infection and plant disease resistance. Key words: Paulownia witches’ broom; chromatin conformation; histone modification; transcription regulation


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