scholarly journals The role of histone tails in nucleosome stability: An electrostatic perspective

2020 ◽  
Vol 18 ◽  
pp. 2799-2809
Author(s):  
Artemi Bendandi ◽  
Alessandro S. Patelli ◽  
Alberto Diaspro ◽  
Walter Rocchia
Keyword(s):  
Histone Tails ◽  
Nucleosome Stability

scholarly journals Effect of histone H4 tail on nucleosome stability and internucleosomal interactions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tommy Stormberg ◽  
Sridhar Vemulapalli ◽  
Shaun Filliaux ◽  
Yuri L. Lyubchenko
Keyword(s):  
Chromatin Structure ◽  
Histone H4 ◽  
Nucleosome Assembly ◽  
Dna Templates ◽  
Histone Tails ◽  
Force Microscopy ◽  
Atomic Force ◽  
Dna Unwrapping ◽  
Nucleosome Stability

AbstractChromatin structure is dictated by nucleosome assembly and internucleosomal interactions. The tight wrapping of nucleosomes inhibits gene expression, but modifications to histone tails modulate chromatin structure, allowing for proper genetic function. The histone H4 tail is thought to play a large role in regulating chromatin structure. Here we investigated the structure of nucleosomes assembled with a tail-truncated H4 histone using Atomic Force Microscopy. We assembled tail-truncated H4 nucleosomes on DNA templates allowing for the assembly of mononucleosomes or dinucleosomes. Mononucleosomes assembled on nonspecific DNA led to decreased DNA wrapping efficiency. This effect is less pronounced for nucleosomes assembled on positioning motifs. Dinucleosome studies resulted in the discovery of two effects- truncation of the H4 tail does not diminish the preferential positioning observed in full-length nucleosomes, and internucleosomal interaction eliminates the DNA unwrapping effect. These findings provide insight on the role of histone H4 in chromatin structure and stability.

scholarly journals Critical Role of Histone Tail Entropy in Nucleosome Unwinding

2018 ◽  
Author(s):  
Bin Zhang ◽  
Thomas Parsons
Keyword(s):  
Genome Stability ◽  
Critical Role ◽  
Dna Unwinding ◽  
Histone Tails ◽  
Dynamical Decoupling ◽  
Physicochemical Interactions ◽  
Advanced Sampling ◽  
Histone Core ◽  
Nucleosome Stability

The nucleosome is the fundamental packaging unit for the genome. It must both remain tightly wound to ensure genome stability while simultaneously being flexible enough to keep the DNA molecule accessible for genome function. The set of physicochemical interactions responsible for the delicate balance between these naturally opposed processes have not been determined due to challenges in resolving partially unwound nucleosome configurations at atomic resolution. Using a near atomistic protein-DNA model and advanced sampling techniques, we calculate the free energy cost of nucleosome DNA unwinding. Our simulations identify a large energetic barrier that decouples the outer and inner DNA unwinding into two separate processes, occurring on different timescales. This dynamical decoupling allows the exposure of outer DNA at a modest cost to ensure accessibility while keeping the inner DNA and the histone core intact to maintain stability. We also reveal that this energetic barrier arises from a delayed loss of contacts between disordered histone tails and the DNA, and is, surprisingly, largely offset by an entropic contribution from these tails. Our study uncovers the balance of energetic and entropic contributions that dictate nucleosome stability, suggesting that tilting this balance may be a previously-unknown mechanism for regulating genome function.

scholarly journals Role of the histone “tails” in the folding of oligonucleosomes depleted of histone H1.

1992 ◽  
Vol 267 (27) ◽  
pp. 19587-19595 ◽  
Author(s):  
M Garcia-Ramirez ◽  
F Dong ◽  
J Ausio
Keyword(s):  
Histone H1 ◽  
Histone Tails

scholarly journals Genetic Analysis of the Role of Pol II Holoenzyme Components in Repression by the Cyc8-Tup1 Corepressor in Yeast

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1535-1542 ◽  
Author(s):  
Mark Lee ◽  
Sukalyan Chatterjee ◽  
Kevin Struhl
Keyword(s):  
Transcriptional Repression ◽  
Detectable Effect ◽  
Genetic Screens ◽  
Phenotypic Analysis ◽  
Histone Tails ◽  
Pol Ii ◽  
Corepressor Complex ◽  
The Individual ◽  
Modest Effect

Abstract The Cyc8-Tup1 corepressor complex is targeted to promoters by pathway-specific DNA-binding repressors, thereby inhibiting the transcription of specific classes of genes. Genetic screens have identified mutations in a variety of Pol II holoenzyme components (Srb8, Srb9, Srb10, Srb11, Sin4, Rgr1, Rox3, and Hrs1) and in the N-terminal tails of histones H3 and H4 that weaken repression by Cyc8-Tup1. Here, we analyze the effect of individual and multiple mutations in many of these components on transcriptional repression of natural promoters that are regulated by Cyc8-Tup1. In all cases tested, individual mutations have a very modest effect on SUC2 RNA levels and no detectable effect on levels of ANB1, MFA2, and RNR2. Furthermore, multiple mutations within the Srb components, between Srbs and Sin4, and between Srbs and histone tails affect Cyc8-Tup1 repression to the same modest extent as the individual mutations. These results argue that the weak effects of the various mutations on repression by Cyc8-Tup1 are not due to redundancy among components of the Pol II machinery, and they argue against a simple redundancy between the holoenzyme and chromatin pathways. In addition, phenotypic analysis indicates that, although Srbs8–11 are indistinguishable with respect to Cyc8-Tup1 repression, the individual Srbs are functionally distinct in other respects. Genetic interactions among srb mutations imply that a balance between the activities of Srb8 + Srb10 and Srb11 is important for normal cell growth.

scholarly journals Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 192
Author(s):  
Siska Van Belle ◽  
Sara El Ashkar ◽  
Kateřina Čermáková ◽  
Filip Matthijssens ◽  
Steven Goossens ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Survival ◽  
Cell Lines ◽  
Protein Interactions ◽  
Leukemic Cell ◽  
Related Protein ◽  
Histone Tails ◽  
Knockout Mouse Model ◽  
Leukemic Cell Lines

HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Derived Growth Factor p75 (LEDGF/p75), which is essential for MLL-rearranged (MLL-r) leukemia but dispensable for hematopoiesis. Sequel to these findings, we investigated the role of HRP-2 in hematopoiesis and MLL-r leukemia. Protein interactions were investigated by co-immunoprecipitation and validated using recombinant proteins in NMR. A systemic knockout mouse model was used to study normal hematopoiesis and MLL-ENL transformation upon the different HRP-2 genotypes. The role of HRP-2 in MLL-r and other leukemic, human cell lines was evaluated by lentiviral-mediated miRNA targeting HRP-2. We demonstrate that MLL and HRP-2 interact through a conserved interface, although this interaction proved less dependent on menin than the MLL-LEDGF/p75 interaction. The systemic HRP-2 knockout mice only revealed an increase in neutrophils in the peripheral blood, whereas the depletion of HRP-2 in leukemic cell lines and transformed primary murine cells resulted in reduced colony formation independently of MLL-rearrangements. In contrast, primary murine HRP-2 knockout cells were efficiently transformed by the MLL-ENL fusion, indicating that HRP-2, unlike LEDGF/p75, is dispensable for the transformation of MLL-ENL leukemogenesis but important for leukemic cell survival.

Asymmetric breathing motions of nucleosomal DNA and the role of histone tails

2017 ◽  
Vol 147 (6) ◽  
pp. 065101 ◽  
Author(s):  
Kaushik Chakraborty ◽  
Sharon M. Loverde
Keyword(s):  
Histone Tails ◽  
Nucleosomal Dna

Epigenetic regulation of adipogenesis by histone-modifying enzymes

Epigenomics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 235-251
Author(s):  
Paolo E Macchia ◽  
Immacolata C Nettore ◽  
Fabiana Franchini ◽  
Laura Santana-Viera ◽  
Paola Ungaro
Keyword(s):  
Epigenetic Regulation ◽  
Transcriptional Control ◽  
Metabolic Diseases ◽  
Epigenetic Mechanisms ◽  
Differentiation Process ◽  
Histone Tails ◽  
Histone Modifying Enzymes ◽  
Epigenomic Regulation ◽  
Adipocyte Development

Many studies investigating the transcriptional control of adipogenesis have been published so far; recently the research is focusing on the role of epigenetic mechanisms in regulating the process of adipocyte development. Histone-modifying enzymes and the histone tails post-transcriptional modifications catalyzed by them, are fundamentally involved in the epigenetic regulation of adipogenesis. In our review, we will discuss recent advances in epigenomic regulation of adipogenesis with a focus on histone-modifying enzymes implicated in the various phases of adipocytes differentiation process from mesenchymal stem cells to mature adipocytes. Understanding adipogenesis, may provide new ways to treat obesity and related metabolic diseases.

Role of Histone Tails in the Conformation and Interactions of Nucleosome Core Particles†

Biochemistry ◽  
2004 ◽  
Vol 43 (16) ◽  
pp. 4773-4780 ◽  
Author(s):  
Aurélie Bertin ◽  
Amélie Leforestier ◽  
Dominique Durand ◽  
Françoise Livolant
Keyword(s):  
Histone Tails ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
Core Particles

scholarly journals Role of Histone N-Terminal Tails and Their Acetylation in Nucleosome Dynamics

2000 ◽  
Vol 20 (19) ◽  
pp. 7230-7237 ◽  
Author(s):  
Violette Morales ◽  
Hélène Richard-Foy
Keyword(s):  
Topoisomerase I ◽  
Globular Domain ◽  
Histone Tail ◽  
Histone Tails ◽  
Nucleosome Dynamics ◽  
Nucleosome Structure ◽  
Left Handed ◽  
Negative Supercoiling ◽  
And Function

ABSTRACT Histone N-terminal tails are central to the processes that modulate nucleosome structure and function. We have studied the contribution of core histone tails to the structure of a single nucleosome and to a histone (H3-H4)2 tetrameric particle assembled on a topologically constrained DNA minicircle. The effect of histone tail cleavage and histone tail acetylation on the structure of the nucleoprotein particle was investigated by analyzing the DNA topoisomer equilibrium after relaxation of DNA torsional stress by topoisomerase I. Removal of the H3 and H4 N-terminal tails, as well as their acetylation, provoked a dramatic change in the linking-number difference of the (H3-H4)2 tetrameric particle, with a release of up to 70% of the negative supercoiling previously constrained by this structure. The (H3-H4)2 tetramers containing tailless or hyperacetylated histones showed a striking preference for relaxed DNA over negatively supercoiled DNA. This argues in favor of a change in tetramer structure that constrains less DNA and adopts a relaxed flat conformation instead of its left-handed conformation within the nucleosome. In contrast neither removal or hyperacetylation of H3 and H4 tails nor removal or hyperacetylation of H2A and H2B N-terminal tails affected the nucleosome structure. This indicates that the globular domain of H2A and H2B is sufficient to stabilize the tailless or the hyperacetylated (H3-H4)2tetramer in a left-handed superhelix conformation. These results suggest that the effect of histone tail acetylation that facilitates transcription may be mediated via transient formation of an (H3-H4)2 tetrameric particle that could adopt an open structure only when H3 and/or H4 tails are hyperacetylated.

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