scholarly journals The H3 Tail Domain Participates in Multiple Interactions during Folding and Self-Association of Nucleosome Arrays

2007 ◽  
Vol 27 (6) ◽  
pp. 2084-2091 ◽  
Author(s):  
Pu-Yeh Kan ◽  
Xu Lu ◽  
Jeffrey C. Hansen ◽  
Jeffrey J. Hayes
Keyword(s):  
Short Range ◽  
Chromatin Condensation ◽  
Cross Linking ◽  
Tail Domain ◽  
Histone Tail ◽  
Linker Histones ◽  
Complex Interactions ◽  
Self Association ◽  
Core Histone Tail ◽  
Nucleosome Arrays

ABSTRACT The core histone tail domains play a central role in chromatin structure and epigenetic processes controlling gene expression. Although little is known regarding the molecular details of tail interactions, it is likely that they participate in both short-range and long-range interactions between nucleosomes. Previously, we demonstrated that the H3 tail domain participates in internucleosome interactions during MgCl2-dependent condensation of model nucleosome arrays. However, these studies did not distinguish whether these internucleosome interactions represented short-range intra-array or longer-range interarray interactions. To better understand the complex interactions of the H3 tail domain during chromatin condensation, we have developed a new site-directed cross-linking method to identify and quantify interarray interactions mediated by histone tail domains. Interarray cross-linking was undetectable under salt conditions that induced only local folding, but was detected concomitant with salt-dependent interarray oligomerization at higher MgCl2 concentrations. Interestingly, lysine-to-glutamine mutations in the H3 tail domain to mimic acetylation resulted in little or no reduction in interarray cross-linking. In contrast, binding of a linker histone caused a much greater enhancement of interarray interactions for unmodified H3 tails compared to “acetylated” H3 tails. Collectively these results indicate that H3 tail domain performs multiple functions during chromatin condensation via distinct molecular interactions that can be differentially regulated by acetylation or binding of linker histones.

scholarly journals The H4 Tail Domain Participates in Intra- and Internucleosome Interactions with Protein and DNA during Folding and Oligomerization of Nucleosome Arrays

2008 ◽  
Vol 29 (2) ◽  
pp. 538-546 ◽  
Author(s):  
Pu-Yeh Kan ◽  
Tamara L. Caterino ◽  
Jeffrey J. Hayes
Keyword(s):  
Tail Domain ◽  
Predominant Role ◽  
Linker Histones ◽  
Histone Fold ◽  
Histone Fold Domain ◽  
Strong Stimulation ◽  
Self Association ◽  
Core Histone Tail ◽  
A Site ◽  
Nucleosome Arrays

ABSTRACT The condensation of nucleosome arrays into higher-order secondary and tertiary chromatin structures likely involves long-range internucleosomal interactions mediated by the core histone tail domains. We have characterized interarray interactions mediated by the H4 tail domain, known to play a predominant role in the formation of such structures. We find that the N-terminal end of the H4 tail mediates interarray contacts with DNA during self-association of oligonucleosome arrays similar to that found previously for the H3 tail domain. However, a site near the histone fold domain of H4 participates in a distinct set of interactions, contacting both DNA and H2A in condensed structures. Moreover, we also find that H4-H2A interactions occur via an intra- as well as an internucleosomal fashion, supporting an additional intranucleosomal function for the tail. Interestingly, acetylation of the H4 tail has little effect on interarray interactions by itself but overrides the strong stimulation of interarray interactions induced by linker histones. Our results indicate that the H4 tail facilitates secondary and tertiary chromatin structure formation via a complex array of potentially exclusive interactions that are distinct from those of the H3 tail domain.

scholarly journals Acetylation Mimics within Individual Core Histone Tail Domains Indicate Distinct Roles in Regulating the Stability of Higher-Order Chromatin Structure

2007 ◽  
Vol 28 (1) ◽  
pp. 227-236 ◽  
Author(s):  
Xiaodong Wang ◽  
Jeffrey J. Hayes
Keyword(s):  
Chromatin Structure ◽  
Higher Order ◽  
Core Histone ◽  
Lysine Acetylation ◽  
Tail Domain ◽  
Histone Tail ◽  
Self Association ◽  
Core Histone Tail ◽  
The Stability ◽  
Nucleosome Arrays

ABSTRACT Nucleosome arrays undergo salt-dependent self-association into large oligomers in a process thought to recapitulate essential aspects of higher-order tertiary chromatin structure formation. Lysine acetylation within the core histone tail domains inhibits self-association, an effect likely related to its role in facilitating transcription. As acetylation of specific tail domains may encode distinct functions, we investigated biochemical and self-association properties of model nucleosome arrays containing combinations of native and mutant core histones with lysine-to-glutamine substitutions to mimic acetylation. Acetylation mimics within the tail domains of H2B and H4 caused the largest inhibition of array self-association, while modification of the H3 tail uniquely affected the stability of DNA wrapping within individual nucleosomes. In addition, the effect of acetylation mimics on array self-association is inconsistent with a simple charge neutralization mechanism. For example, acetylation mimics within the H2A tail can have either a positive or negative effect on self-association, dependent upon the acetylation state of the other tails and nucleosomal repeat length. Finally, we demonstrate that glutamine substitutions and lysine acetylation within the H4 tail domain have identical effects on nucleosome array self-association. Our results indicate that acetylation of specific tail domains plays distinct roles in the regulation of chromatin structure.

Reversible Oligonucleosome Self-Association:  Dependence on Divalent Cations and Core Histone Tail Domains†

Biochemistry ◽  
1996 ◽  
Vol 35 (13) ◽  
pp. 4009-4015 ◽  
Author(s):  
Patricia M. Schwarz ◽  
Alicia Felthauser ◽  
Terace M. Fletcher ◽  
Jeffrey C. Hansen
Keyword(s):  
Divalent Cations ◽  
Core Histone ◽  
Histone Tail ◽  
Self Association ◽  
Core Histone Tail

scholarly journals Reversible chromatin condensation by the DNA repair and demethylation factor thymine DNA glycosylase

2021 ◽  
Author(s):  
Charles E Deckard ◽  
Jonathan T Sczepanski
Keyword(s):  
Dna Repair ◽  
Chromatin Condensation ◽  
Methylation Status ◽  
Dna Demethylation ◽  
Dna Glycosylase ◽  
New Paradigm ◽  
Thymine Dna Glycosylase ◽  
Terminal Domain ◽  
Self Association ◽  
Nucleosome Arrays

Abstract Chromatin structures (and modulators thereof) play a central role in genome organization and function. Herein, we report that thymine DNA glycosylase (TDG), an essential enzyme involved in DNA repair and demethylation, has the capacity to alter chromatin structure directly through its physical interactions with DNA. Using chemically defined nucleosome arrays, we demonstrate that TDG induces decompaction of individual chromatin fibers upon binding and promotes self-association of nucleosome arrays into higher-order oligomeric structures (i.e. condensation). Chromatin condensation is mediated by TDG’s disordered polycationic N-terminal domain, whereas its C-terminal domain antagonizes this process. Furthermore, we demonstrate that TDG-mediated chromatin condensation is reversible by growth arrest and DNA damage 45 alpha (GADD45a), implying that TDG cooperates with its binding partners to dynamically control chromatin architecture. Finally, we show that chromatin condensation by TDG is sensitive to the methylation status of the underlying DNA. This new paradigm for TDG has specific implications for associated processes, such as DNA repair, DNA demethylation, and transcription, and general implications for the role of DNA modification ‘readers’ in controlling chromatin organization.

scholarly journals Persistent Interactions of Core Histone Tails with Nucleosomal DNA following Acetylation and Transcription Factor Binding

1998 ◽  
Vol 18 (11) ◽  
pp. 6293-6304 ◽  
Author(s):  
Vesco Mutskov ◽  
Delphine Gerber ◽  
Dimitri Angelov ◽  
Juan Ausio ◽  
Jerry Workman ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Biology ◽  
Binding Sites ◽  
Cross Linking ◽  
Uv Laser ◽  
Histone Tail ◽  
Histone Tails ◽  
Nucleosomal Dna ◽  
Core Histones

ABSTRACT In this study, we examined the effect of acetylation of the NH2 tails of core histones on their binding to nucleosomal DNA in the absence or presence of bound transcription factors. To do this, we used a novel UV laser-induced protein-DNA cross-linking technique, combined with immunochemical and molecular biology approaches. Nucleosomes containing one or five GAL4 binding sites were reconstituted with hypoacetylated or hyperacetylated core histones. Within these reconstituted particles, UV laser-induced histone-DNA cross-linking was found to occur only via the nonstructured histone tails and thus presented a unique tool for studying histone tail interactions with nucleosomal DNA. Importantly, these studies demonstrated that the NH2 tails were not released from nucleosomal DNA upon histone acetylation, although some weakening of their interactions was observed at elevated ionic strengths. Moreover, the binding of up to five GAL4-AH dimers to nucleosomes occupying the central 90 bp occurred without displacement of the histone NH2 tails from DNA. GAL4-AH binding perturbed the interaction of each histone tail with nucleosomal DNA to different degrees. However, in all cases, greater than 50% of the interactions between the histone tails and DNA was retained upon GAL4-AH binding, even if the tails were highly acetylated. These data illustrate an interaction of acetylated or nonacetylated histone tails with DNA that persists in the presence of simultaneously bound transcription factors.

scholarly journals A Distinct Switch in Interactions of the Histone H4 Tail Domain upon Salt-dependent Folding of Nucleosome Arrays

2014 ◽  
Vol 289 (39) ◽  
pp. 27342-27351 ◽  
Author(s):  
Sharon Pepenella ◽  
Kevin J. Murphy ◽  
Jeffrey J. Hayes
Keyword(s):  
Tail Domain ◽  
Histone H4 ◽  
Nucleosome Arrays

scholarly journals RanGTP induces an effector gradient of XCTK2 and importin α/β for spindle microtubule cross-linking

2019 ◽  
Author(s):  
Stephanie C. Ems-McClung ◽  
Mackenzie Emch ◽  
Stephanie Zhang ◽  
Serena Mahnoor ◽  
Lesley N. Weaver ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Spindle Assembly ◽  
Cross Linking ◽  
Tail Domain ◽  
Inhibitory Effects ◽  
Cross Link ◽  
Spindle Microtubule ◽  
Spindle Poles ◽  
Importin Α ◽  
Combined Actions

AbstractHigh RanGTP around chromatin is important for governing spindle assembly during meiosis and mitosis by releasing the inhibitory effects of importin α/β. Here we examine how the Ran gradient regulates Kinesin-14 function to control spindle organization. We show that Xenopus Kinesin-14, XCTK2, and importin α/β form an effector gradient, which is highest at the poles that diminishes toward the chromatin and is inverse of the RanGTP gradient. Importin α/β preferentially inhibit XCTK2 anti-parallel microtubule cross-linking and sliding by decreasing the microtubule affinity of the XCTK2 tail domain. This change in microtubule affinity enables RanGTP to target endogenous XCTK2 to the spindle. We propose that these combined actions of the Ran pathway are critical to promote Kinesin-14 parallel microtubule cross-linking at the spindle poles to cluster centrosomes in cancer cells. Furthermore, our work illustrates that RanGTP regulation in the spindle is not simply a switch, but rather generates effector gradients where RanGTP gradually tunes the activities of spindle assembly factors.SummaryEms-McClung et al. visualize a RanGTP effector gradient of association between XCTK2 and importin α/β in the spindle. The importins preferentially inhibit XCTK2-mediate anti-parallel microtubule cross-linking and sliding, which allows XCTK2 to cross-link parallel microtubules and help focus spindle poles.

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