Chromatin structure of eukaryotic promoters: a changing perspective

2002 ◽  
Vol 80 (3) ◽  
pp. 295-300 ◽  
Author(s):  
Philippe T Georgel

Over the past few years, many studies have attempted to determine the role of nucleosomes as both positive and negative transcription regulators. The emphasis has mostly centered on chromatin remodeling activities and histone modifications, leaving the question of the influence of the higher-order structure out of the spotlight. Recent technical developments allowing direct measurements of size and mechanical properties of in vivo assembled chromatin may shed light on this poorly understood area. This article presents a brief summary of the current knowledge on transcription-dependent chromatin dynamics and how a rather simple agarose electrophoresis method may change the current view on structural changes linked to transcriptional activation of chromatin.Key words: chromatin, higher-order structure, quantitative agarose gel electrophoresis.

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.


2021 ◽  
Author(s):  
Halida Thanveer Asana Marican ◽  
Hongyuan Shen

Metaphase-based cytogenetic methods based on scoring of chromosome aberrations for the estimation of the radiation dose received provide a powerful approach for evaluating the associated risk upon radiation exposure and form the bulk of our current knowledge of radiation-induced chromosome damages. They mainly rely on inducing quiescent peripheral lymphocytes into proliferation and blocking them at metaphases to quantify the damages at the chromosome level. However, human organs and tissues demonstrate various sensitivity towards radiation and within them, self-proliferating progenitor/stem cells are believed to be the most sensitive populations. The radiation-induced chromosome aberrations in these cells remain largely unknown, especially in the context of an intact living organism. Zebrafish is an ideal animal model for research into this aspect due to their small size and the large quantities of progenitor cells present during the embryonic stages. In this study, we employ a novel metaphase-based cytogenetic approach on zebrafish embryos and demonstrate that chromosome-type and chromatid-type aberrations could be identified in progenitor cells at different cell-cycle stages at the point of radiation exposure. Our work positions zebrafish at the forefront as a useful animal model for studying radiation-induced chromosome structural changes in vivo.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jing Li ◽  
Jordan T White ◽  
Harry Saavedra ◽  
James O Wrabl ◽  
Hesam N Motlagh ◽  
...  

Intrinsically disordered proteins (IDPs) present a functional paradox because they lack stable tertiary structure, but nonetheless play a central role in signaling, utilizing a process known as allostery. Historically, allostery in structured proteins has been interpreted in terms of propagated structural changes that are induced by effector binding. Thus, it is not clear how IDPs, lacking such well-defined structures, can allosterically affect function. Here, we show a mechanism by which an IDP can allosterically control function by simultaneously tuning transcriptional activation and repression, using a novel strategy that relies on the principle of ‘energetic frustration’. We demonstrate that human glucocorticoid receptor tunes this signaling in vivo by producing translational isoforms differing only in the length of the disordered region, which modulates the degree of frustration. We expect this frustration-based model of allostery will prove to be generally important in explaining signaling in other IDPs.


2018 ◽  
Vol 29 (13) ◽  
pp. 1652-1663 ◽  
Author(s):  
Shujun Cai ◽  
Yajiao Song ◽  
Chen Chen ◽  
Jian Shi ◽  
Lu Gan

The 30-nm fiber is commonly formed by oligonucleosome arrays in vitro but rarely found inside cells. To determine how chromatin higher-order structure is controlled, we used electron cryotomography (cryo-ET) to study the undigested natural chromatin released from two single-celled organisms in which 30-nm fibers have not been observed in vivo: picoplankton and yeast. In the presence of divalent cations, most of the chromatin from both organisms is condensed into a large mass in vitro. Rare irregular 30-nm fibers, some of which include face-to-face nucleosome interactions, do form at the periphery of this mass. In the absence of divalent cations, picoplankton chromatin decondenses into open zigzags. By contrast, yeast chromatin mostly remains condensed, with very few open motifs. Yeast chromatin packing is largely unchanged in the absence of linker histone and mildly decondensed when histones are more acetylated. Natural chromatin is therefore generally nonpermissive of regular motifs, even at the level of oligonucleosomes.


2019 ◽  
Vol 63 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Thomas O. Tolsma ◽  
Jeffrey C. Hansen

Abstract The dynamic structure of chromatin is linked to gene regulation and many other biological functions. Consequently, it is of importance to understand the factors that regulate chromatin dynamics. While the in vivo analysis of chromatin has verified that histone post-translational modifications play a role in modulating DNA accessibility, the complex nuclear environment and multiplicity of modifications prevents clear conclusions as to how individual modifications influence chromatin dynamics in the cell. For this reason, in vitro analyses of model reconstituted nucleosomal arrays has been pivotal in understanding the dynamic nature of chromatin compaction and the affects that specific post-translational modifications can have on the higher order chromatin structure. In this mini-review, we briefly describe the dynamic chromatin structures that have been observed in vitro and the environmental conditions that give rise to these various conformational states. Our focus then turns to a discussion of the specific histone post-translational modifications that have been shown to alter formation of these higher order chromatin structures in vitro and how this may relate to the biological state and accessibility of chromatin in vivo.


2020 ◽  
Author(s):  
Lei Chang ◽  
Mengfan Li ◽  
Shipeng Shao ◽  
Chen Li ◽  
Shanshan Ai ◽  
...  

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.


2010 ◽  
Vol 11 (6) ◽  
pp. 703-716 ◽  
Author(s):  
Janeth Alva-Medina ◽  
Myrna A. R. Dent ◽  
Armando Aranda-Anzaldo

2015 ◽  
Vol 396 (12) ◽  
pp. 1325-1337 ◽  
Author(s):  
Csilla Patasi ◽  
Jana Godočíková ◽  
Soňa Michlíková ◽  
Yan Nie ◽  
Radka Káčeriková ◽  
...  

Abstract Septins are a family of conserved cytoskeletal proteins playing an essential role in cytokinesis and in many other cellular processes in fungi and animals. In budding yeast Saccharomyces cerevisiae, septins form filaments and higher-order structures at the mother-bud neck depending on the particular stage of the cell cycle. Septin structures at the division plane serve as a scaffold to recruit the proteins required for particular cellular processes. The formation and localization of septin structures at particular stages of the cell cycle also determine functionality of these proteins. Many different proteins participate in regulating septin assembly. Despite recent developments, we are only beginning to understand how specific protein-protein interactions lead to changes in the polymerization of septin filaments or assembly of higher-order structures. Here, using fluorescence and electron microscopy, we found that Bni5 crosslinks septin filaments into networks by bridging pairs or multiple filaments, forming structures that resemble railways. Furthermore, Bni5 appears to be a substrate of the Elm1 protein kinase in vitro. Moreover, Elm1 induces in the presence of Bni5 disassembly of long septin filaments, suggesting that these proteins may participate in the hourglass to double ring transition. This work gives new insight into the regulatory role of Bni5 in the structural changes of septins.


2019 ◽  
Author(s):  
Lei Chang ◽  
Mengfan Li ◽  
Shipeng Shao ◽  
Boxin Xue ◽  
Yingping Hou ◽  
...  

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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