HMGN dynamics and chromatin function

2003 ◽  
Vol 81 (3) ◽  
pp. 113-122 ◽  
Author(s):  
Frédéric Catez ◽  
Jae-Hwan Lim ◽  
Robert Hock ◽  
Yuri V Postnikov ◽  
Michael Bustin
Keyword(s):  
Binding Sites ◽  
Protein Composition ◽  
Nuclear Proteins ◽  
Chromatin Interactions ◽  
Binding Partners ◽  
Nucleosomal Dna ◽  
Transient Interactions ◽  
And Function ◽  
Nucleosome Binding

Recent studies indicate that most nuclear proteins, including histone H1 and HMG are highly mobile and their interaction with chromatin is transient. These findings suggest that the structure of chromatin is dynamic and the protein composition at any particular chromatin site is not fixed. Here we discuss how the dynamic behavior of the nucleosome binding HMGN proteins affects the structure and function of chromatin. The high intranuclear mobility of HMGN insures adequate supply of protein throughout the nucleus and serves to target these proteins to their binding sites. Transient interactions of the proteins with nucleosomes destabilize the higher order chromatin, enhance the access to nucleosomal DNA, and impart flexibility to the chromatin fiber. While roaming the nucleus, the HMGN proteins encounter binding partners and form metastable multiprotein complexes, which modulate their chromatin interactions. Studies with HMGN proteins underscore the important role of protein dynamics in chromatin function.Key words: HMG, nuclear proteins, chromatin, HMGN.

scholarly journals Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative.

1995 ◽  
Vol 15 (3) ◽  
pp. 1405-1421 ◽  
Author(s):  
C C Adams ◽  
J L Workman
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Sites ◽  
Specific Binding ◽  
General Mechanism ◽  
Nf Kappa B ◽  
Nucleosomal Dna ◽  
Nucleosome Binding

To investigate mechanisms by which multiple transcription factors access complex promoters and enhancers within cellular chromatin, we have analyzed the binding of disparate factors to nucleosome cores. We used a purified in vitro system to analyze binding of four activator proteins, two GAL4 derivatives, USF, and NF-kappa B (KBF1), to reconstituted nucleosome cores containing different combinations of binding sites. Here we show that binding of any two or all three of these factors to nucleosomal DNA is inherently cooperative. Thus, the binuclear Zn clusters of GAL4, the helix-loop-helix/basic domains of USF, and the rel domain of NF-kappa B all participated in cooperative nucleosome binding, illustrating that this effect is not restricted to a particular DNA-binding domain. Simultaneous binding by two factors increased the affinity of individual factors for nucleosomal DNA by up to 2 orders of magnitude. Importantly, cooperative binding resulted in efficient nucleosome binding by factors (USF and NF-kappa B) which independently possess little nucleosome-binding ability. The participation of GAL4 derivatives in cooperative nucleosome binding required only DNA-binding and dimerization domains, indicating that disruption of histone-DNA contacts by factor binding was responsible for the increased affinity of additional factors. Cooperative nucleosome binding required sequence-specific binding of all transcription factors, appeared to have spatial constraints, and was independent of the orientation of the binding sites on the nucleosome. These results indicate that cooperative nucleosome binding is a general mechanism that may play a significant role in loading complex enhancer and promoter elements with multiple diverse factors in chromatin and contribute to the generation of threshold responses and transcriptional synergy by multiple activator sites in vivo.

scholarly journals Triplex target sites of MEG3 RNA-chromatin interactions

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 76
Author(s):  
Ivan Antonov ◽  
Yulia A. Medvedeva
Keyword(s):  
Chromatin Structure ◽  
Binding Sites ◽  
Noncoding Rnas ◽  
Long Distance ◽  
Chromatin Interactions ◽  
Target Sites ◽  
Dna Triplex ◽  
3D Chromatin Structure ◽  
Genomic Locations

Many long noncoding RNAs are bound to chromatin. MEG3 binds to multiple different genomic locations, containing GA-rich motifs, and form RNA-DNA triplex structures. In this work, we test whether the MEG3 binding sites are specific enough to be regulated by a particular lncRNA. We show that at least in the case of MEG3, a subset of the triplex target sites (TTS) is able to hybridize with various different RNAs almost irrespectively of their sequences. Nowadays, the role of chromatin bound RNAs in the formation of 3D chromatin structure is actively discussed. We speculate that such universal TTSs may contribute to establishing long-distance chromosomal contacts.

Muscular dystrophies, dilated cardiomyopathy, lipodystrophy and neuropathy: the nuclear connection

2002 ◽  
Vol 4 (17) ◽  
pp. 1-21 ◽  
Author(s):  
Stephen L. Maidment ◽  
Juliet A. Ellis
Keyword(s):  
Dilated Cardiomyopathy ◽  
Nuclear Proteins ◽  
Muscular Dystrophies ◽  
Lamin A ◽  
Cell Integrity ◽  
Distinct Disease ◽  
Life Threatening ◽  
And Function ◽  
Disease Understanding

An understanding of muscle structure and function is central to improving our knowledge of the group of muscle diseases referred to as muscular dystrophies. These diseases involve a progressive weakening and wasting of skeletal muscle, which can be associated with life-threatening cardiac arrhythmias. The vast majority of these diseases arise from defects in either cytoskeletal or structural proteins, resulting in a breakdown of muscle cell integrity. However, mutations in two nuclear proteins – emerin and lamin A/C – have also been demonstrated to give rise to a muscular dystrophy phenotype. In addition, mutations in lamin A/C can give rise to a dilated cardiomyopathy, a lipodystrophy or a neuropathy. It is far from clear how mutations in nuclear proteins can result in a dystrophy, or cause more than one clinically distinct disease. Understanding the functional role of nuclear proteins in causing these diseases will therefore provide novel insights into muscle function, and should hopefully provide new directions for treatment.

scholarly journals The yeast SWI-SNF complex facilitates binding of a transcriptional activator to nucleosomal sites in vivo.

1997 ◽  
Vol 17 (8) ◽  
pp. 4811-4819 ◽  
Author(s):  
L G Burns ◽  
C L Peterson
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Protein Assembly ◽  
Transcriptional Activators ◽  
Regulate Gene Expression ◽  
Activation Of Transcription ◽  
Free Region ◽  
And Function

The Saccharomyces cerevisiae SWI-SNF complex is a 2-MDa protein assembly that is required for the function of many transcriptional activators. Here we describe experiments on the role of the SWI-SNF complex in activation of transcription by the yeast activator GAL4. We find that while SWI-SNF activity is not required for the GAL4 activator to bind to and activate transcription from nucleosome-free binding sites, the complex is required for GAL4 to bind to and function at low-affinity, nucleosomal binding sites in vivo. This SWI-SNF dependence can be overcome by (i) replacing the low-affinity sites with higher-affinity, consensus GAL4 binding sequences or (ii) placing the low-affinity sites into a nucleosome-free region. These results define the criteria for the SWI-SNF dependence of gene expression and provide the first in vivo evidence that the SWI-SNF complex can regulate gene expression by modulating the DNA binding of an upstream activator protein.

scholarly journals Mucosal glycan degradation of the host by the gut microbiota

Glycobiology ◽  
2020 ◽  
Author(s):  
Andrew Bell ◽  
Nathalie Juge
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Binding Sites ◽  
Short Review ◽  
Commensal Bacteria ◽  
Glycoside Hydrolases ◽  
Safe Distance ◽  
Human Gut ◽  
And Function

Abstract The gut microbiota plays a major role in human health and an alteration in gut microbiota structure and function has been implicated in several diseases. In the colon, mucus covering the epithelium is critical to maintain a homeostatic relationship with the gut microbiota by harboring a microbial community at safe distance from the epithelium surface. The mucin glycans composing the mucus layer provide binding sites and a sustainable source of nutrients to the bacteria inhabiting the mucus niche. Access to these glycan chains requires a complement of glycoside hydrolases (GHs) produced by bacteria across the phyla constituting the human gut microbiota. Due to the increased recognition of the role of mucus-associated microbes in human health, how commensal bacteria breakdown and utilize host mucin glycans has become of increased interest and is reviewed here. This short review provides an overview of the strategies evolved by gut commensal bacteria to access this rich source of the nutrient with a focus on the GHs involved in mucin degradation.

scholarly journals Role of the histone amino termini in facilitated binding of a transcription factor, GAL4-AH, to nucleosome cores.

1994 ◽  
Vol 14 (2) ◽  
pp. 970-981 ◽  
Author(s):  
M Vettese-Dadey ◽  
P Walter ◽  
H Chen ◽  
L J Juan ◽  
J L Workman
Keyword(s):  
Dna Binding ◽  
Binding Sites ◽  
Core Histone ◽  
Nucleosome Core ◽  
Naked Dna ◽  
The Core ◽  
Nucleosomal Dna ◽  
Multiple Binding Sites ◽  
Multiple Binding

Facilitated, "cooperative" binding of GAL4-AH to nucleosomal DNA occurred in response to inhibition from the core histone amino termini. The binding of GAL4-AH (which contains the DNA-binding and dimerization domains of GAL4) to nucleosome cores containing multiple binding sites initiated at the end of a nucleosome core and proceeded in a cooperative manner until all sites were occupied. However, following tryptic removal of the core histone amino termini, GAL4-AH binding appeared to be noncooperative, similar to binding naked DNA. Binding of GAL4-AH to nucleosomes bearing a single GAL4 site at different positions indicated that inhibition of GAL4 binding was largely mediated by the histone amino termini and primarily occurred at sites well within the core and not near the end. When the histone amino termini were intact, binding of GAL4-AH to sites near the center of a nucleosome core was greatly enhanced by the presence of additional GAL4 dimers bound to more-accessible positions. These data illustrate that the binding of a factor to more-accessible sites, near the end of a nucleosome, allows facilitated binding of additional factors to the center of the nucleosome, thereby overcoming repression from the core histone amino termini. This mechanism may contribute to the binding of multiple factors to complex promoter and enhancer elements in cellular chromatin.

scholarly journals Systematic screening of CTCF binding partners identifies that BHLHE40 regulates CTCF genome-wide distribution and long-range chromatin interactions

2020 ◽  
Vol 48 (17) ◽  
pp. 9606-9620
Author(s):  
Gongcheng Hu ◽  
Xiaotao Dong ◽  
Shixin Gong ◽  
Yawei Song ◽  
Andrew P Hutchins ◽  
...  
Keyword(s):  
Binding Sites ◽  
Wide Distribution ◽  
Ctcf Binding ◽  
Loop Formation ◽  
Systematic Screening ◽  
Chromatin Interactions ◽  
Binding Partners ◽  
Number Of Factors ◽  
Genome Wide ◽  
Localization Analysis

Abstract CTCF plays a pivotal role in mediating chromatin interactions, but it does not do so alone. A number of factors have been reported to co-localize with CTCF and regulate CTCF loops, but no comprehensive analysis of binding partners has been performed. This prompted us to identify CTCF loop participants and regulators by co-localization analysis with CTCF. We screened all factors that had ChIP-seq data in humans by co-localization analysis with human super conserved CTCF (hscCTCF) binding sites, and identified many new factors that overlapped with hscCTCF binding sites. Combined with CTCF loop information, we observed that clustered factors could promote CTCF loops. After in-depth mining of each factor, we found that many factors might have the potential to promote CTCF loops. Our data further demonstrated that BHLHE40 affected CTCF loops by regulating CTCF binding. Together, this study revealed that many factors have the potential to participate in or regulate CTCF loops, and discovered a new role for BHLHE40 in modulating CTCF loop formation.

scholarly journals Transfer RNA Genes Affect Chromosome Structure and Function via Local Effects

2018 ◽  
Author(s):  
Omar Hamdani ◽  
Namrita Dhillon ◽  
Tsung-Han S. Hsieh ◽  
Takahiro Fujita ◽  
Josefina Ocampo ◽  
...  
Keyword(s):  
Long Range ◽  
Binding Sites ◽  
Transfer Rna ◽  
Chromosome Architecture ◽  
Architectural Proteins ◽  
Random Manner ◽  
And Function ◽  
Chromosome Tethering ◽  
Rna Genes

AbstractThe genome is packaged and organized in an ordered, non-random manner and specific chromatin segments contact nuclear substructures to mediate this organization. While transfer RNA genes (tDNAs) are essential for the generation of tRNAs, these loci are also binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the role of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacks any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromosome folding or chromosome tethering. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long range HML-HMR heterochromatin clustering. We propose that the tDNAs primarily affect local chromatin structure that result in effects on long-range chromosome architecture.

scholarly journals G-quadruplexes offer a conserved structural motif for NONO recruitment to NEAT1 architectural lncRNA

2020 ◽  
Author(s):  
Eric A J Simko ◽  
Honghe Liu ◽  
Tao Zhang ◽  
Adan Velasquez ◽  
Shraddha Teli ◽  
...  
Keyword(s):  
Binding Sites ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Structural Features ◽  
Structural Motif ◽  
Non Coding Rna ◽  
G Quadruplex ◽  
And Function ◽  
Long Non Coding Rna

Abstract The long non-coding RNA NEAT1 serves as a scaffold for the assembly of paraspeckles, membraneless nuclear organelles involved in gene regulation. Paraspeckle assembly requires NEAT1 recruitment of the RNA-binding protein NONO, however the NEAT1 elements responsible for recruitment are unknown. Herein we present evidence that previously unrecognized structural features of NEAT1 serve an important role in these interactions. Led by the initial observation that NONO preferentially binds the G-quadruplex conformation of G-rich C9orf72 repeat RNA, we find that G-quadruplex motifs are abundant and conserved features of NEAT1. Furthermore, we determine that NONO binds NEAT1 G-quadruplexes with structural specificity and provide evidence that G-quadruplex motifs mediate NONO-NEAT1 association, with NONO binding sites on NEAT1 corresponding largely to G-quadruplex motifs, and treatment with a G-quadruplex-disrupting small molecule causing dissociation of native NONO-NEAT1 complexes. Together, these findings position G-quadruplexes as a primary candidate for the NONO-recruiting elements of NEAT1 and provide a framework for further investigation into the role of G-quadruplexes in paraspeckle formation and function.

scholarly journals RcaE-Dependent Regulation of Carboxysome Structural Proteins Has a Central Role in Environmental Determination of Carboxysome Morphology and Abundance in Fremyella diplosiphon

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Brandon A. Rohnke ◽  
Shailendra P. Singh ◽  
Bagmi Pattanaik ◽  
Beronda L. Montgomery
Keyword(s):  
Carbon Fixation ◽  
Protein Composition ◽  
Limited Attention ◽  
Fremyella Diplosiphon ◽  
Chromatic Acclimation ◽  
And Function ◽  
Organismal Fitness ◽  
Protein Shell

Carboxysomes are proteinaceous subcellular compartments, or bacterial organelles, found in cyanobacteria that consist of a protein shell surrounding a core primarily composed of the enzyme ribulose-1,5-biphosphate carboxylase/oxygenase (RuBisCO) that is central to the carbon dioxide-concentrating mechanism (CCM) and carbon fixation. Whereas significant insights have been gained regarding the structure and synthesis of carboxysomes, limited attention has been given to how their size, abundance, and protein composition are regulated to ensure optimal carbon fixation in dynamic environments. Given the centrality of carboxysomes in photosynthesis, we provide an analysis of the role of a photoreceptor, RcaE, which functions in matching photosynthetic pigmentation to the external environment during complementary chromatic acclimation and thereby optimizing photosynthetic efficiency, in regulating carboxysome dynamics. Our data highlight a role for RcaE in perceiving external light cues and regulating carboxysome structure and function and, thus, in the cellular capacity for carbon fixation and organismal fitness.

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