scholarly journals SMARCAD1 is an ATP-dependent histone octamer exchange factor with de novo nucleosome assembly activity

2021 ◽  
Vol 7 (42) ◽  
Author(s):  
Jonathan Markert ◽  
Keda Zhou ◽  
Karolin Luger
Keyword(s):  
De Novo ◽  
Nucleosome Assembly ◽  
Exchange Factor ◽  
Histone Octamer ◽  
Assembly Activity

scholarly journals Structure and function of the chromatin remodeler SMARCAD1 with its nucleosome substrate

2021 ◽  
Author(s):  
Jonathan Markert ◽  
Keda Zhou ◽  
Karolin Luger
Keyword(s):  
De Novo ◽  
Structure And Function ◽  
Dependent Manner ◽  
Nucleosome Assembly ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Histone Octamer ◽  
Disease Information ◽  
Unique Manner ◽  
And Function

AbstractThe ATP-dependent chromatin remodeler SMARCAD1 acts on nucleosomes during DNA repair and transcription, but despite its implication in disease, information on its structure and function is scarce. Chromatin remodelers use a variety of ways to engage nucleosomes, and outcomes of the ATP-dependent reactions vary widely. Here we show that SMARCAD1 transfers the entire histone octamer from one DNA segment to another in an ATP-dependent manner but is also capable of de novo nucleosome assembly from histone octamer, due to its ability to bind all histones simultaneously. We describe the cryoEM structure of SMARCAD1 in complex with a nucleosome and show that it engages its substrate unlike any other chromatin remodeler. Our combined data allow us to put forward a testable model for SMARCAD1 mechanism.One-Sentence SummaryThe single subunit chromatin remodeler SMARCAD1 engages nucleosomes in a unique manner and transfers the entire histone octamer.

scholarly journals Distinct histone H3–H4 binding modes of sNASP reveal the basis for cooperation and competition of histone chaperones

2021 ◽  
Author(s):  
Chao-Pei Liu ◽  
Wenxing Jin ◽  
Jie Hu ◽  
Mingzhu Wang ◽  
Jingjing Chen ◽  
...  
Keyword(s):  
De Novo ◽  
Critical Role ◽  
Histone H3 ◽  
Coiled Coil ◽  
Dynamic Network ◽  
Histone Chaperones ◽  
Binding Modes ◽  
Nucleosome Assembly ◽  
Partially Unfolded

Chromosomal duplication requires de novo assembly of nucleosomes from newly synthesized histones, and the process involves a dynamic network of interactions between histones and histone chaperones. sNASP and ASF1 are two major histone H3–H4 chaperones found in distinct and common complexes, yet how sNASP binds H3–H4 in the presence and absence of ASF1 remains unclear. Here we show that, in the presence of ASF1, sNASP principally recognizes a partially unfolded Nα region of histone H3, and in the absence of ASF1, an additional sNASP binding site becomes available in the core domain of the H3–H4 complex. Our study also implicates a critical role of the C-terminal tail of H4 in the transfer of H3–H4 between sNASP and ASF1 and the coiled-coil domain of sNASP in nucleosome assembly. These findings provide mechanistic insights into coordinated histone binding and transfer by histone chaperones.

scholarly journals Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity

2017 ◽  
Vol 26 (23) ◽  
pp. 4728-4740 ◽  
Author(s):  
Sara M Katrancha ◽  
Yi Wu ◽  
Minsheng Zhu ◽  
Betty A Eipper ◽  
Anthony J Koleske ◽  
...  
Keyword(s):  
De Novo ◽  
Sequence Variants ◽  
Factor Activity ◽  
De Novo Mutations ◽  
Exchange Factor ◽  
Neurodevelopmental Disease ◽  
Rare Sequence

scholarly journals Structure of a single-chain H2A/H2B dimer

2020 ◽  
Vol 76 (5) ◽  
pp. 194-198
Author(s):  
Christopher Warren ◽  
Jeffrey B. Bonanno ◽  
Steven C. Almo ◽  
David Shechter
Keyword(s):  
Chromatin Remodeling ◽  
Interacting Proteins ◽  
Structural Studies ◽  
Histone H2a ◽  
Nucleosome Assembly ◽  
Single Chain ◽  
Histone Octamer ◽  
C Terminus ◽  
Histone Dimers ◽  
Histone Modifying Enzymes

Chromatin is the complex assembly of nucleic acids and proteins that makes up the physiological form of the eukaryotic genome. The nucleosome is the fundamental repeating unit of chromatin, and is composed of ∼147 bp of DNA wrapped around a histone octamer formed by two copies of each core histone: H2A, H2B, H3 and H4. Prior to nucleosome assembly, and during histone eviction, histones are typically assembled into soluble H2A/H2B dimers and H3/H4 dimers and tetramers. A multitude of factors interact with soluble histone dimers and tetramers, including chaperones, importins, histone-modifying enzymes and chromatin-remodeling enzymes. It is still unclear how many of these proteins recognize soluble histones; therefore, there is a need for new structural tools to study non-nucleosomal histones. Here, a single-chain, tailless Xenopus H2A/H2B dimer was created by directly fusing the C-terminus of H2B to the N-terminus of H2A. It is shown that this construct (termed scH2BH2A) is readily expressed in bacteria and can be purified under non-denaturing conditions. A 1.31 Å resolution crystal structure of scH2BH2A shows that it adopts a conformation that is nearly identical to that of nucleosomal H2A/H2B. This new tool is likely to facilitate future structural studies of many H2A/H2B-interacting proteins.

scholarly journals The histone chaperone FACT modulates nucleosome structure by tethering its components

2018 ◽  
Vol 1 (4) ◽  
pp. e201800107 ◽  
Author(s):  
Tao Wang ◽  
Yang Liu ◽  
Garrett Edwards ◽  
Daniel Krzizike ◽  
Hataichanok Scherman ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Histone Chaperone ◽  
Nucleosome Assembly ◽  
Transcription Elongation Factor ◽  
Nucleosome Structure ◽  
Mechanistic Insight ◽  
Nucleosome Formation ◽  
Nucleosome Disassembly ◽  
Assembly Activity ◽  
Insight Into

Human FAcilitates Chromatin Transcription (hFACT) is a conserved histone chaperone that was originally described as a transcription elongation factor with potential nucleosome assembly functions. Here, we show that FACT has moderate tetrasome assembly activity but facilitates H2A–H2B deposition to form hexasomes and nucleosomes. In the process, FACT tethers components of the nucleosome through interactions with H2A–H2B, resulting in a defined intermediate complex comprising FACT, a histone hexamer, and DNA. Free DNA extending from the tetrasome then competes FACT off H2A–H2B, thereby promoting hexasome and nucleosome formation. Our studies provide mechanistic insight into how FACT may stabilize partial nucleosome structures during transcription or nucleosome assembly, seemingly facilitating both nucleosome disassembly and nucleosome assembly.

scholarly journals Histone supply regulates S phase timing and cell cycle progression

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Ufuk Günesdogan ◽  
Herbert Jäckle ◽  
Alf Herzig
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
De Novo ◽  
S Phase ◽  
Histone Genes ◽  
Nucleosome Assembly ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
A Cell ◽  
Surveillance Mechanism

Eukaryotes package DNA into nucleosomes that contain a core of histone proteins. During DNA replication, nucleosomes are disrupted and re-assembled with newly synthesized histones and DNA. Despite much progress, it is still unclear why higher eukaryotes contain multiple core histone genes, how chromatin assembly is controlled, and how these processes are coordinated with cell cycle progression. We used a histone null mutation of Drosophila melanogaster to show that histone supply levels, provided by a defined number of transgenic histone genes, regulate the length of S phase during the cell cycle. Lack of de novo histone supply not only extends S phase, but also causes a cell cycle arrest during G2 phase, and thus prevents cells from entering mitosis. Our results suggest a novel cell cycle surveillance mechanism that monitors nucleosome assembly without involving the DNA repair pathways and exerts its effect via suppression of CDC25 phosphatase String expression.

scholarly journals The Nucleosome Assembly Activity of NAP1 Is Enhanced by Alien

2007 ◽  
Vol 27 (10) ◽  
pp. 3557-3568 ◽  
Author(s):  
Maren Eckey ◽  
Wei Hong ◽  
Maria Papaioannou ◽  
Aria Baniahmad
Keyword(s):  
Gene Expression ◽  
Chromatin Immunoprecipitation ◽  
Hormone Receptors ◽  
Nucleosome Assembly ◽  
Nucleosome Assembly Protein ◽  
Nucleosome Assembly Protein 1 ◽  
Dna Template ◽  
Assembly Activity

ABSTRACT The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitamin D receptor (VDR), binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. Furthermore, Alien reduces the accessibility of the histones H3 and H4 for NAP1-promoted assembly reaction. This indicates that Alien sustains and reinforces the formation of nucleosomes. Employing deletion mutants of Alien suggests that different regions of Alien are involved in enhancement of NAP1-mediated nucleosome assembly and in inhibiting the accessibility of the histones H3 and H4. In addition, we provide evidence that Alien is associated with chromatin and with micrococcus nuclease-prepared nucleosome fractions and interacts with the histones H3 and H4. Furthermore, chromatin immunoprecipitation and reimmunoprecipitation experiments suggest that NAP1 and Alien localize to the endogenous CYP24 promoter in vivo, a VDR target gene. Based on these findings, we present here a novel pathway linking corepressor function with nucleosome assembly activity.

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