scholarly journals CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly

2020 ◽  
Vol 133 (15) ◽  
pp. jcs243303 ◽  
Author(s):  
Koichiro Otake ◽  
Jun-ichirou Ohzeki ◽  
Nobuaki Shono ◽  
Kazuto Kugou ◽  
Koei Okazaki ◽  
...  
Keyword(s):  
De Novo ◽  
Artificial Chromosome ◽  
Human Artificial Chromosome ◽  
Open Chromatin ◽  
Histone Chaperones ◽  
Satellite Dnas ◽  
Chromatin States ◽  
Heterochromatin Formation ◽  
Acidic Domain ◽  
Alphoid Dna

ABSTRACTCENP-B binds to CENP-B boxes on centromeric satellite DNAs (known as alphoid DNA in humans). CENP-B maintains kinetochore function through interactions with CENP-A nucleosomes and CENP-C. CENP-B binding to transfected alphoid DNA can induce de novo CENP-A assembly, functional centromere and kinetochore formation, and subsequent human artificial chromosome (HAC) formation. Furthermore, CENP-B also facilitates H3K9 (histone H3 lysine 9) trimethylation on alphoid DNA, mediated by Suv39h1, at ectopic alphoid DNA integration sites. Excessive heterochromatin invasion into centromere chromatin suppresses CENP-A assembly. It is unclear how CENP-B controls such different chromatin states. Here, we show that the CENP-B acidic domain recruits histone chaperones and many chromatin modifiers, including the H3K36 methylase ASH1L, as well as the heterochromatin components Suv39h1 and HP1 (HP1α, β and γ, also known as CBX5, CBX1 and CBX3, respectively). ASH1L facilitates the formation of open chromatin competent for CENP-A assembly on alphoid DNA. These results indicate that CENP-B is a nexus for histone modifiers that alternatively promote or suppress CENP-A assembly by mutually exclusive mechanisms. Besides the DNA-binding domain, the CENP-B acidic domain also facilitates CENP-A assembly de novo on transfected alphoid DNA. CENP-B therefore balances CENP-A assembly and heterochromatin formation on satellite DNA.

scholarly journals Antagonising Chromatin Remodelling Activities in the Regulation of Mammalian Ribosomal Transcription

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 961
Author(s):  
Kanwal Tariq ◽  
Ann-Kristin Östlund Farrants
Keyword(s):  
Stress Responses ◽  
Ribosomal Gene ◽  
Chromatin Remodelling ◽  
Chromatin State ◽  
Rrna Gene ◽  
Open Chromatin ◽  
Histone Chaperones ◽  
Embryonic Cells ◽  
Cell Type ◽  
Chromatin States

Ribosomal transcription constitutes the major energy consuming process in cells and is regulated in response to proliferation, differentiation and metabolic conditions by several signalling pathways. These act on the transcription machinery but also on chromatin factors and ncRNA. The many ribosomal gene repeats are organised in a number of different chromatin states; active, poised, pseudosilent and repressed gene repeats. Some of these chromatin states are unique to the 47rRNA gene repeat and do not occur at other locations in the genome, such as the active state organised with the HMG protein UBF whereas other chromatin state are nucleosomal, harbouring both active and inactive histone marks. The number of repeats in a certain state varies on developmental stage and cell type; embryonic cells have more rRNA gene repeats organised in an open chromatin state, which is replaced by heterochromatin during differentiation, establishing different states depending on cell type. The 47S rRNA gene transcription is regulated in different ways depending on stimulus and chromatin state of individual gene repeats. This review will discuss the present knowledge about factors involved, such as chromatin remodelling factors NuRD, NoRC, CSB, B-WICH, histone modifying enzymes and histone chaperones, in altering gene expression and switching chromatin states in proliferation, differentiation, metabolic changes and stress responses.

scholarly journals 391. De Novo Human Artificial Chromosome Formation Is Predetermined by Initial Chromatin Assembly and Transcriptional Patterns after Transfection

2006 ◽  
Vol 13 ◽  
pp. S149
Author(s):  
Hiroshi Nakashima ◽  
Megumi Nakano ◽  
Ryoko Ohnishi ◽  
Yasushi Hiraoka ◽  
Yasufumi Kaneda ◽  
...  
Keyword(s):  
De Novo ◽  
Artificial Chromosome ◽  
Chromatin Assembly ◽  
Human Artificial Chromosome ◽  
Chromosome Formation

scholarly journals Organization of Synthetic Alphoid DNA Array in Human Artificial Chromosome (HAC) with a Conditional Centromere

2012 ◽  
Vol 1 (12) ◽  
pp. 590-601 ◽  
Author(s):  
Natalay Kouprina ◽  
Alexander Samoshkin ◽  
Indri Erliandri ◽  
Megumi Nakano ◽  
Hee-Sheung Lee ◽  
...  
Keyword(s):  
Artificial Chromosome ◽  
Human Artificial Chromosome ◽  
Dna Array ◽  
Alphoid Dna

scholarly journals CENP-B box is required for de novo centromere chromatin assembly on human alphoid DNA

2002 ◽  
Vol 159 (5) ◽  
pp. 765-775 ◽  
Author(s):  
Jun-ichirou Ohzeki ◽  
Megumi Nakano ◽  
Teruaki Okada ◽  
Hiroshi Masumoto
Keyword(s):  
Dna Sequence ◽  
Dna Sequences ◽  
De Novo ◽  
Repetitive Sequences ◽  
Point Mutations ◽  
Artificial Chromosome ◽  
Binding Activity ◽  
Chromatin Assembly ◽  
Direct Assembly ◽  
Alphoid Dna

Centromere protein (CENP) B boxes, recognition sequences of CENP-B, appear at regular intervals in human centromeric α-satellite DNA (alphoid DNA). In this study, to determine whether information carried by the primary sequence of alphoid DNA is involved in assembly of functional human centromeres, we created four kinds of synthetic repetitive sequences: modified alphoid DNA with point mutations in all CENP-B boxes, resulting in loss of all CENP-B binding activity; unmodified alphoid DNA containing functional CENP-B boxes; and nonalphoid repetitive DNA sequences with or without functional CENP-B boxes. These four synthetic repetitive DNAs were introduced into cultured human cells (HT1080), and de novo centromere assembly was assessed using the mammalian artificial chromosome (MAC) formation assay. We found that both the CENP-B box and the alphoid DNA sequence are required for de novo MAC formation and assembly of functional centromere components such as CENP-A, CENP-C, and CENP-E. Using the chromatin immunoprecipitation assay, we found that direct assembly of CENP-A and CENP-B in cells with synthetic alphoid DNA required functional CENP-B boxes. To the best of our knowledge, this is the first reported evidence of a functional molecular link between a centromere-specific DNA sequence and centromeric chromatin assembly in humans.

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.

scholarly journals H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory

2020 ◽  
Vol 133 (14) ◽  
pp. jcs242610 ◽  
Author(s):  
Nuno M. C. Martins ◽  
Fernanda Cisneros-Soberanis ◽  
Elisa Pesenti ◽  
Natalia Y. Kochanova ◽  
Wei-Hao Shang ◽  
...  
Keyword(s):  
De Novo ◽  
Artificial Chromosome ◽  
Human Artificial Chromosome ◽  
Chimeric Proteins ◽  
Epigenetic Memory ◽  
Chromatin Signature ◽  
Protein Levels ◽  
Centromere Function ◽  
Histone 3

ABSTRACTMost eukaryotic centromeres are located within heterochromatic regions. Paradoxically, heterochromatin can also antagonize de novo centromere formation, and some centromeres lack it altogether. In order to investigate the importance of heterochromatin at centromeres, we used epigenetic engineering of a synthetic alphoidtetO human artificial chromosome (HAC), to which chimeric proteins can be targeted. By tethering the JMJD2D demethylase (also known as KDM4D), we removed heterochromatin mark H3K9me3 (histone 3 lysine 9 trimethylation) specifically from the HAC centromere. This caused no short-term defects, but long-term tethering reduced HAC centromere protein levels and triggered HAC mis-segregation. However, centromeric CENP-A was maintained at a reduced level. Furthermore, HAC centromere function was compatible with an alternative low-H3K9me3, high-H3K27me3 chromatin signature, as long as residual levels of H3K9me3 remained. When JMJD2D was released from the HAC, H3K9me3 levels recovered over several days back to initial levels along with CENP-A and CENP-C centromere levels, and mitotic segregation fidelity. Our results suggest that a minimal level of heterochromatin is required to stabilize mitotic centromere function but not for maintaining centromere epigenetic memory, and that a homeostatic pathway maintains heterochromatin at centromeres.This article has an associated First Person interview with the first authors of the paper.

scholarly journals Inferring time series chromatin states for promoter-enhancer pairs based on Hi-C data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Henriette Miko ◽  
Yunjiang Qiu ◽  
Bjoern Gaertner ◽  
Maike Sander ◽  
Uwe Ohler
Keyword(s):  
Time Series ◽  
Histone Modifications ◽  
Gene Activation ◽  
Expectation Maximization Algorithm ◽  
Chromatin State ◽  
Open Chromatin ◽  
Multiple Time ◽  
Enhancer Activity ◽  
Chromatin States ◽  
Multiple Time Points

Abstract Background Co-localized combinations of histone modifications (“chromatin states”) have been shown to correlate with promoter and enhancer activity. Changes in chromatin states over multiple time points (“chromatin state trajectories”) have previously been analyzed at promoter and enhancers separately. With the advent of time series Hi-C data it is now possible to connect promoters and enhancers and to analyze chromatin state trajectories at promoter-enhancer pairs. Results We present TimelessFlex, a framework for investigating chromatin state trajectories at promoters and enhancers and at promoter-enhancer pairs based on Hi-C information. TimelessFlex extends our previous approach Timeless, a Bayesian network for clustering multiple histone modification data sets at promoter and enhancer feature regions. We utilize time series ATAC-seq data measuring open chromatin to define promoters and enhancer candidates. We developed an expectation-maximization algorithm to assign promoters and enhancers to each other based on Hi-C interactions and jointly cluster their feature regions into paired chromatin state trajectories. We find jointly clustered promoter-enhancer pairs showing the same activation patterns on both sides but with a stronger trend at the enhancer side. While the promoter side remains accessible across the time series, the enhancer side becomes dynamically more open towards the gene activation time point. Promoter cluster patterns show strong correlations with gene expression signals, whereas Hi-C signals get only slightly stronger towards activation. The code of the framework is available at https://github.com/henriettemiko/TimelessFlex. Conclusions TimelessFlex clusters time series histone modifications at promoter-enhancer pairs based on Hi-C and it can identify distinct chromatin states at promoter and enhancer feature regions and their changes over time.

Alphoid DNA from different chromosomes forms de novo minichromosomes with high efficiency

2005 ◽  
Vol 13 (4) ◽  
pp. 411-422 ◽  
Author(s):  
T. Kaname ◽  
A. McGuigan ◽  
A. Georghiou ◽  
Y. Yurov ◽  
K. Osoegawa ◽  
...  
Keyword(s):  
High Efficiency ◽  
De Novo ◽  
Alphoid Dna
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