Molecular insights into α‐Synuclein interaction with individual human core histones, linker histone, and dsDNA

2021 ◽  
Author(s):  
Sneha Jos ◽  
Hemanga Gogoi ◽  
Thazhe Kootteri Prasad ◽  
Manjunath A. Hurakadli ◽  
Neelagandan Kamariah ◽  
...  
Keyword(s):  
Linker Histone ◽  
Core Histones ◽  
Individual Human

scholarly journals Site-specific ubiquitylation acts as a regulator of linker histone H1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eva Höllmüller ◽  
Simon Geigges ◽  
Marie L. Niedermeier ◽  
Kai-Michael Kammer ◽  
Simon M. Kienle ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Histone H1 ◽  
Linker Histone ◽  
Active Chromatin ◽  
Site Specific ◽  
Linker Histone H1 ◽  
Fundamental Process ◽  
Core Histones ◽  
Wide Scale

AbstractDecoding the role of histone posttranslational modifications (PTMs) is key to understand the fundamental process of epigenetic regulation. This is well studied for PTMs of core histones but not for linker histone H1 in general and its ubiquitylation in particular due to a lack of proper tools. Here, we report on the chemical synthesis of site-specifically mono-ubiquitylated H1.2 and identify its ubiquitin-dependent interactome on a proteome-wide scale. We show that site-specific ubiquitylation of H1 at position K64 modulates interactions with deubiquitylating enzymes and the deacetylase SIRT1. Moreover, it affects H1-dependent chromatosome assembly and phase separation resulting in a more open chromatosome conformation generally associated with a transcriptionally active chromatin state. In summary, we propose that site-specific ubiquitylation plays a general regulatory role for linker histone H1.

scholarly journals Signals in chicken beta-globin DNA influence chromatin assembly in vitro.

1993 ◽  
Vol 13 (12) ◽  
pp. 7596-7603 ◽  
Author(s):  
K Liu ◽  
J D Lauderdale ◽  
A Stein
Keyword(s):  
Intergenic Region ◽  
Globin Gene ◽  
Linker Histone ◽  
Chromatin Assembly ◽  
Beta Globin ◽  
Erythroid Cells ◽  
Core Histones ◽  
Histone H5 ◽  
In Erythroid Cells

We have confirmed the result that chicken beta-globin gene chromatin, which possesses the characteristics of active chromatin in erythroid cells, has shortened internucleosome spacings compared with bulk chromatin or that of the ovalbumin gene, which is inactive. To understand how the short (approximately 180-bp) nucleosome repeat arises specifically on beta-globin DNA, we have studied chromatin assembly of cloned chicken beta-globin DNA in a defined in vitro system. With chicken erythrocyte core histones and linker histone H5 as the only cellular components, a cloned 6.2-kb chicken beta-globin DNA fragment assembled into chromatin possessing a regular 180 +/- 5-bp repeat, very similar to what is observed in erythroid cells. A 2-kb DNA subfragment containing the beta A gene and promoter region, but lacking the downstream intergenic region between the beta A and epsilon genes, failed to generate a regular nucleosome array in vitro, suggesting that the intergenic region facilitates linker histone-induced nucleosome alignment. When the beta A gene was placed on a plasmid that contained a known chromatin-organizing signal, nucleosome alignment with a 180-bp periodicity was restored, whereas nucleosomes on flanking plasmid sequences possessed a 210-bp spacing periodicity. Our results suggest that the shortened 180-bp nucleosome spacing periodicity observed in erythroid cells is encoded in the beta-globin DNA sequence and that nucleosome alignment by linker histones is facilitated by sequences in the beta A-epsilon intergenic region.

scholarly journals Remodeling sperm chromatin in Xenopus laevis egg extracts: the role of core histone phosphorylation and linker histone B4 in chromatin assembly.

1994 ◽  
Vol 126 (3) ◽  
pp. 591-601 ◽  
Author(s):  
S Dimitrov ◽  
M C Dasso ◽  
A P Wolffe
Keyword(s):  
Xenopus Laevis ◽  
Sperm Nucleus ◽  
Linker Histone ◽  
Core Histone ◽  
Sperm Chromatin ◽  
Histone Phosphorylation ◽  
Egg Extracts ◽  
Core Histones ◽  
Histone Octamers

We find that the remodeling of the condensed Xenopus laevis sperm nucleus into the paternal pronucleus in egg extracts is associated with phosphorylation of the core histones H2A, H2A.X and H4, and uptake of a linker histone B4 and a HMG 2 protein. Histone B4 is required for the assembly of chromatosome structures in the pronucleus. However neither B4 nor core histone phosphorylation are required for the assembly of spaced nucleosomal arrays. We suggest that the spacing of nucleosomal arrays is determined by interaction between adjacent histone octamers under physiological assembly conditions.

scholarly journals Phosphorylated and dephosphorylated linker histone H1 reside in distinct chromatin domains in Tetrahymena macronuclei.

1995 ◽  
Vol 6 (8) ◽  
pp. 1077-1087 ◽  
Author(s):  
M J Lu ◽  
S S Mpoke ◽  
C A Dadd ◽  
C D Allis
Keyword(s):  
High Performance ◽  
Gene Activation ◽  
Linker Histone ◽  
Active Chromatin ◽  
Chromatin Decondensation ◽  
Physiological Conditions ◽  
Evolutionarily Conserved ◽  
Core Histones ◽  
Dense Chromatin ◽  
Step Mechanism

Phosphorylated and dephosphorylated isoforms of Tetrahymena macronuclear H1 were separated from each other by cation-exchange high performance liquid chromatography and used to generate a pairwise set of antisera that discriminate the phosphorylation state of this linker histone. Affinity-purified antibodies from each sera recognize appropriate H1 isoforms and stain macronuclei under appropriate physiological conditions. Immunogold localizations demonstrate that phosphorylated and dephosphorylated H1 localize nonrandomly in distinct subdomains of macronuclear chromatin. Dephosphorylated H1 is strongly enriched in the electron-dense chromatin bodies that punctuate macronuclear chromatin. In contrast, phosphorylated H1 isoforms, as well as an evolutionarily conserved H2A.F/Z-like variant (hv1) believed to function in the establishment of transcriptionally competent chromatin, are modestly enriched at the periphery of chromatin bodies and in the surrounding euchromatin. Using antibodies against TATA-binding protein, we show that transcriptionally active chromatin lies outside of the chromatin bodies in an area relatively devoid of H1. Antibodies against general core histones are more or less evenly distributed across these domains. Together, these data are consistent with a model in which phosphorylation of H1, perhaps in association with hv1, loosens the binding of H1 in chromatin leading to chromatin decondensation as part of a first-step mechanism in gene activation. In contrast, our data support the view that dephosphorylation of this linker histone facilitates or stabilizes condensed, transcriptionally silent chromatin.

scholarly journals Linker histone dH1K27 dimethylation marks Drosophila heterochromatin independently of H3K9 methylation

2021 ◽  
Author(s):  
Jordi Bernues ◽  
Andrea Izquierdo-Boulstridge ◽  
Oscar Reina Garcia ◽  
Lucia Castejon ◽  
Elena Fernandez-Castaner ◽  
...  
Keyword(s):  
Linker Histone ◽  
Epigenetic Mark ◽  
Dna Repeats ◽  
H3k9 Methylation ◽  
Satellite Dnas ◽  
Chromatin States ◽  
Heterochromatin Formation ◽  
Core Histones ◽  
Drosophila Heterochromatin ◽  
Dna Elements

Post-translational modifications (PTMs) of histones are important epigenetic determinants and specific core histones PTMs correlate with functional chromatin states. However, despite linker histone H1s are heavily post-translationally modified, little is known about the genomic distribution of H1s PTMs and their association with epigenetic chromatin states. Here, we address this question in Drosophila that encodes a single somatic linker histone, dH1. We previously reported that dH1 is dimethylated at K27 (dH1K27me2). Here, we show that dH1K27me2 is a major PTM of Drosophila heterochromatin. At mitosis, dH1K27me2 accumulates at pericentromeric heterochromatin, while, in interphase cells, it is also detected at intercalary heterochromatin. ChIPseq experiments show that dH1K27me2 enriched regions cluster at both the assembled and unassembled heterochromatin regions of all four Drosophila chromosomes. More than 98% of the dH1K27me2 enriched regions map to heterochromatic repetitive DNA elements, including transposable elements, simple DNA repeats and satellite DNAs. We also show that dH1K27me2 is independent of H3K9 methylation, as it is equally detected in flies carrying a H3K9R mutation. Moreover, dH1K27me2 is not affected by depletion of Su(var)3-9, HP1a and Su(var)4-20. Altogether these results suggest that dH1K27me2 is a novel epigenetic mark of Drosophila heterochromatin that acts upstream of the major Su(var)3- 9/HP1a pathway of heterochromatin formation.

Chromatin structures condensed by linker histones

2019 ◽  
Vol 63 (1) ◽  
pp. 75-87 ◽  
Author(s):  
Bing-Rui Zhou ◽  
Yawen Bai
Keyword(s):  
Structural Unit ◽  
Linker Histone ◽  
Histone H2a ◽  
Linker Histones ◽  
The Core ◽  
High Order Chromatin Structure ◽  
Core Histones ◽  
Order Structures ◽  
Made In

Abstract In eukaryotic cells, genomic DNA exists in the form of chromatin through association with histone proteins, which consist of four core histone (H2A, H2B, H3, and H4) families and one linker histone (H1) family. The core histones bind to DNA to form the nucleosome, the recurring structural unit of chromatin. The linker histone binds to the nucleosome to form the next structural unit of chromatin, the chromatosome, which occurs dominantly in metazoans. Linker histones also play an essential role in condensing chromatin to form higher order structures. Unlike the core histones in the formation of the nucleosome, the role of linker histone in the formation of the chromatosome and high-order chromatin structure is not well understood. Nevertheless, exciting progress in the structural studies of chromatosomes and nucleosome arrays condensed by linker histones has been made in the last several years. In this mini-review, we discuss these recent experimental results and provide some perspectives for future studies.

Signals in chicken beta-globin DNA influence chromatin assembly in vitro

1993 ◽  
Vol 13 (12) ◽  
pp. 7596-7603
Author(s):  
K Liu ◽  
J D Lauderdale ◽  
A Stein
Keyword(s):  
Intergenic Region ◽  
Globin Gene ◽  
Linker Histone ◽  
Chromatin Assembly ◽  
Beta Globin ◽  
Erythroid Cells ◽  
Core Histones ◽  
Histone H5 ◽  
In Erythroid Cells

We have confirmed the result that chicken beta-globin gene chromatin, which possesses the characteristics of active chromatin in erythroid cells, has shortened internucleosome spacings compared with bulk chromatin or that of the ovalbumin gene, which is inactive. To understand how the short (approximately 180-bp) nucleosome repeat arises specifically on beta-globin DNA, we have studied chromatin assembly of cloned chicken beta-globin DNA in a defined in vitro system. With chicken erythrocyte core histones and linker histone H5 as the only cellular components, a cloned 6.2-kb chicken beta-globin DNA fragment assembled into chromatin possessing a regular 180 +/- 5-bp repeat, very similar to what is observed in erythroid cells. A 2-kb DNA subfragment containing the beta A gene and promoter region, but lacking the downstream intergenic region between the beta A and epsilon genes, failed to generate a regular nucleosome array in vitro, suggesting that the intergenic region facilitates linker histone-induced nucleosome alignment. When the beta A gene was placed on a plasmid that contained a known chromatin-organizing signal, nucleosome alignment with a 180-bp periodicity was restored, whereas nucleosomes on flanking plasmid sequences possessed a 210-bp spacing periodicity. Our results suggest that the shortened 180-bp nucleosome spacing periodicity observed in erythroid cells is encoded in the beta-globin DNA sequence and that nucleosome alignment by linker histones is facilitated by sequences in the beta A-epsilon intergenic region.

The site of binding of linker histone to the nucleosome does not depend upon the amino termini of core histones

Biochimie ◽  
1999 ◽  
Vol 81 (7) ◽  
pp. 727-732 ◽  
Author(s):  
Woojin An ◽  
Jordanka Zlatanova ◽  
Sanford H. Leuba ◽  
Kensal van Holde
Keyword(s):  
Linker Histone ◽  
Core Histones

scholarly journals Nucleosome binding by the polymerase I transactivator upstream binding factor displaces linker histone H1.

1997 ◽  
Vol 17 (10) ◽  
pp. 5833-5842 ◽  
Author(s):  
M Kermekchiev ◽  
J L Workman ◽  
C S Pikaard
Keyword(s):  
Histone H1 ◽  
Linker Histone ◽  
Micrococcal Nuclease ◽  
Rrna Genes ◽  
Rrna Gene ◽  
Nucleosome Core ◽  
Binding Factor ◽  
Core Histones ◽  
Upstream Binding Factor ◽  
Polymerase I

Upstream binding factor (UBF) is a vertebrate RNA polymerase I transcription factor that can bend and wrap DNA. To investigate UBF's likely role as an architectural protein of rRNA genes organized in chromatin, we tested UBF's ability to bind rRNA gene enhancers assembled into nucleosome cores (DNA plus core histones) and nucleosomes (DNA plus core histones plus histone H1). UBF bound with low affinity to nucleosome cores formed with enhancer DNA probes of 162 bp. However, on nucleosome cores which contained approximately 60 bp of additional linker DNA, UBF bound with high affinity similar to its binding to naked DNA, forming a ternary DNA-core histone-UBF complex. UBF could be stripped from ternary complexes with competitor DNA to liberate nucleosome cores, rather than free DNA, suggesting that UBF binding to nucleosome cores does not displace the core histones H2A, H2B, H3, and H4. DNase I, micrococcal nuclease, and exonuclease III footprinting suggests that UBF and histone H1 interact with DNA on both sides flanking the histone octamer. Footprinting shows that UBF outcompetes histone H1 for binding to a nucleosome core and will displace, if not dissociate, H1 from its binding site on a preassembled nucleosome. These data suggest that UBF may act to prevent or reverse the assembly of transcriptionally inactive chromatin structures catalyzed by linker histone binding.

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