Chromatin regulators: weaving epigenetic nets

2010 ◽  
Vol 1 (3-4) ◽  
pp. 225-238 ◽  
Author(s):  
Inmaculada Hernández-Muñoz
Keyword(s):  
Nucleosome Position ◽  
Histone Variants ◽  
Cellular Memory ◽  
Intrinsic Signals ◽  
Differentiated Cells ◽  
Chromatin Regulators ◽  
Genome Wide ◽  
Chromatin Regulator ◽  
A Genome ◽  
Multicellular Organisms

AbstractIn multicellular organisms differentiated cells must maintain their cellular memory, which will be faithfully inherited and maintained by their progeny. In addition, these specialized cells are exposed to specific environmental and cell-intrinsic signals and will have to appropriately respond to them. Some of these stimuli lead to changes in a subset of genes or to a genome-wide reprogramming of the cells that will remain after stimuli removal and, in some instances, will be inherited by the daughter cells. The molecular substrate that integrates cellular memory and plasticity is the chromatin, a complex of DNA and histones unique to eukaryotes. The nucleosome is the fundamental unit of the chromatin and nucleosomal organization defines different chromatin conformations. Chromatin regulators affect chromatin conformation and accessibility by covalently modifying the DNA or the histones, substituting histone variants, remodeling the nucleosome position or modulating chromatin looping and folding. These regulators frequently act in multiprotein complexes and highly specific interplays among chromatin marks and different chromatin regulators allow a remarkable array of possibilities. Therefore, chromatin regulator nets act to propagate the conformation of different chromatin regions through DNA replication and mitosis, and to remodel the chromatin fiber to regulate the accessibility of the DNA to transcription factors and to the transcription and repair machineries. Here, the state-of-the-art of the best-known chromatin regulators is reviewed.

scholarly journals Genome-wide decoupling of H2Aub and H3K27me3 in early mouse development

2021 ◽  
Author(s):  
Yezhang Zhu ◽  
Jiali Yu ◽  
Yan Rong ◽  
Yun-Wen Wu ◽  
Heng-Yu Fan ◽  
...  
Keyword(s):  
Polycomb Group ◽  
Mammalian Development ◽  
Mouse Development ◽  
Chromatin Regulators ◽  
Genome Wide ◽  
A Genome ◽  
Independent Functions ◽  
Preimplantation Mouse ◽  
Early Mouse ◽  
Early Mammalian Development

Polycomb group (PcG) proteins are crucial chromatin regulators during development. H2Aub and H3K27me3 are catalyzed by Polycomb-repressive Complex 1 and 2 (PRC1/2) respectively, and largely overlap in the genome due to mutual recruitment of the two complexes. However, whether PRC1/H2Aub and PRC2/H3K27me3 can function independently remains obscure. Here we uncovered a genome-wide decoupling of H2Aub and H3K27me3 in preimplantation mouse embryos, at both canonical PcG targets and broad distal domains. H2Aub represses future bivalent genes without H3K27me3 but does not contribute to maintenance of H3K27me3-dependent non-canonical imprinting. Our study thus revealed their distinct and independent functions in early mammalian development.

scholarly journals Experimental and Bioinformatic upgrade for genome-wide mapping of nucleosomes in Trypanosoma cruzi

2021 ◽  
Author(s):  
Paula Beati ◽  
Milena Massimino Stepnicka ◽  
Salome Vilchez Larrea ◽  
Guillermo Daniel Alonso ◽  
Josefina Ocampo
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Cycle Progression ◽  
Repetitive Sequences ◽  
Nucleosome Position ◽  
Regulatory Elements ◽  
Histone Variants ◽  
Chromatin Organization ◽  
Micrococcal Nuclease ◽  
Cell Manipulation ◽  
Genome Wide

In Trypanosoma cruzi, as in every eukaryotic cell, DNA is packaged into chromatin by octamers of histone proteins that constitute nucleosomes. Besides compacting DNA, nucleosomes control DNA dependent processes by modulating the access of DNA binding proteins to regulatory elements on the DNA; or by providing the platform for additional layers of regulation given by histone variants and histone post-translational modifications. In trypanosomes, protein coding genes are constitutively transcribed as polycistronic units. Therefore, gene expression is controlled mainly post transcriptionally. However, chromatin organization and the histone code influence transcription, cell cycle progression, replication and DNA repair. Hence, determining nucleosome position is of uppermost importance to understand the peculiarities of these processes in trypanosomes. Digestion of chromatin with micrococcal nuclease followed by deep sequencing has been widely applied for genome-wide mapping of nucleosomes in several organisms. Nonetheless, this parasite presents numerous singularities. On one hand, special growth conditions and cell manipulation are required. On the other hand, chromatin organization shows some uniqueness that demands a specially designed analytical approach. An additional entanglement is given by the nature of its genome harboring a large content of repetitive sequences and the poor quality of the genome assembly and annotation of many strains. Here, we adapted this broadly used method to the hybrid reference strain, CL Brener. Particularly, we developed an exhaustive and thorough computational workflow for data analysis, highlighting the relevance of using its whole genome as a reference instead of the commonly used Esmeraldo-like haplotype. Moreover, the performance of two aligners, Bowtie2 and HISAT2 was tested to find the most appropriate tool to map any genomic read to reference genomes bearing this complexity.

scholarly journals The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands

2021 ◽  
Vol 7 (20) ◽  
pp. eabf2229
Author(s):  
Bastian Stielow ◽  
Yuqiao Zhou ◽  
Yinghua Cao ◽  
Clara Simon ◽  
Hans-Martin Pogoda ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Cpg Islands ◽  
Winged Helix ◽  
Sam Domain ◽  
Genome Wide ◽  
Chromatin Regulator ◽  
A Genome ◽  
Dna Elements ◽  
Regulatory Dna ◽  
Winged Helix Domain

CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.

scholarly journals Conserved Transcription Factors Control Chromatin Accessibility and Gene Expression to Maintain Cell Fate Stability and Restrict Reprogramming of Differentiated Cells

2021 ◽  
Author(s):  
Maria A. Missinato ◽  
Sean A. Murphy ◽  
Michaela Lynott ◽  
Anaïs Kervadec ◽  
Michael S. Yu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Large Scale ◽  
Heart Function ◽  
Human Fibroblasts ◽  
Chromatin Accessibility ◽  
Disease States ◽  
Differentiated Cells ◽  
Gene Testing ◽  
Genome Wide ◽  
A Genome

The comprehensive characterization of mechanisms safeguarding cell fate identity in differentiated cells is crucial for 1) our understanding of how differentiation is maintained in healthy tissues or misregulated in disease states and 2) to improve our ability to use direct reprogramming for regenerative purposes. To uncover novel fate-stabilizing regulators, we employed a genome-wide TF siRNA screen followed by a high-complexity combinatorial evaluation of top performing hits, in a cardiac reprogramming assay in mouse embryonic fibroblasts, and subsequently validated our findings in cardiac, neuronal and iPSCs reprogramming assays in primary human fibroblasts and adult endothelial cells. This approach identified a conserved set of 4 TFs (ATF7IP, JUNB, SP7, and ZNF207 [AJSZ]) that robustly opposes cell fate reprogramming, as demonstrated by up to 6-fold increases in efficiency upon AJSZ knockdown in both lineage- and cell type-independent manners. Mechanistically, ChIP-seq and single-cell ATAC-seq analyses, revealed that AJSZ bind to both open and closed chromatin in a genome-wide and regionalized fashion, thereby limiting reprogramming TFs access to target DNA and ability to remodel the chromatin. In parallel, integration of ChIP-seq and RNA-seq data followed by systematic functional gene testing, identified that AJSZ also promote cell fate stability by proximally downregulating a conserved set of genes involved in the regulation of cell fate specification (MEF2C), proteome remodeling (TPP1, PPIC), ATP homeostasis (EFHD1), and inflammation signaling (IL7R), thereby limiting cells ability to undergo large-scale phenotypic changes. Finally, simultaneous knock-down of AJSZ in combination with cardiac reprogramming TFs overexpression improved heart function by 250% as compared to no treatment and 50% as compared to MGT, 1 month after myocardial infarction. In sum, this study uncovers a novel evolutionarily conserved mechanism mediating cell fate stability in differentiated cells and also identifies AJSZ as promising therapeutic targets for regenerative purposes in adult organs

scholarly journals Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico

2019 ◽  
Author(s):  
Takahiro Nakamura ◽  
Muhamad Fahmi ◽  
Jun Tanaka ◽  
Kaito Seki ◽  
Yukihiro Kubota ◽  
...  
Keyword(s):  
Biological Diversity ◽  
Glycoside Hydrolases ◽  
Data Driven ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Class 1 ◽  
And Function ◽  
Multicellular Organisms ◽  
Disordered Regions

Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases. Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function. Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy, and KEGG databases. Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3), and eukaryotes (Class 4). The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively. The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases. These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.

scholarly journals Genome-Wide Distribution of MacroH2A1 Histone Variants in Mouse Liver Chromatin

2010 ◽  
Vol 30 (23) ◽  
pp. 5473-5483 ◽  
Author(s):  
Lakshmi N. Changolkar ◽  
Geetika Singh ◽  
Kairong Cui ◽  
Joel B. Berletch ◽  
Keji Zhao ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Histone Variants ◽  
Wide Distribution ◽  
X Inactivation ◽  
Local Concentration ◽  
Inactive X Chromosome ◽  
Genome Wide ◽  
A Genome ◽  
High Throughput Dna Sequencing ◽  
Liver Chromatin

ABSTRACT Studies of macroH2A histone variants indicate that they have a role in regulating gene expression. To identify direct targets of the macroH2A1 variants, we produced a genome-wide map of the distribution of macroH2A1 nucleosomes in mouse liver chromatin using high-throughput DNA sequencing. Although macroH2A1 nucleosomes are widely distributed across the genome, their local concentration varies over a range of 100-fold or more. The transcribed regions of most active genes are depleted of macroH2A1, often in sharply localized domains that show depletion of 4-fold or more relative to bulk mouse liver chromatin. We used macroH2A1 enrichment to help identify genes that appear to be directly regulated by macroH2A1 in mouse liver. These genes functionally cluster in the area of lipid metabolism. All but one of these genes has increased expression in macroH2A1 knockout mice, indicating that macroH2A1 functions primarily as a repressor in adult liver. This repressor activity is further supported by the substantial and relatively uniform macroH2A1 enrichment along the inactive X chromosome, which averages 4-fold. Genes that escape X inactivation stand out as domains of macroH2A1 depletion. The rarity of such genes indicates that few genes escape X inactivation in mouse liver, in contrast to what has been observed in human cells.

scholarly journals Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico

2019 ◽  
Vol 20 (24) ◽  
pp. 6290 ◽  
Author(s):  
Takahiro Nakamura ◽  
Muhamad Fahmi ◽  
Jun Tanaka ◽  
Kaito Seki ◽  
Yukihiro Kubota ◽  
...  
Keyword(s):  
Biological Diversity ◽  
Glycoside Hydrolases ◽  
Data Driven ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Class 1 ◽  
And Function ◽  
Multicellular Organisms ◽  
Disordered Regions

Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases. Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function. Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases. Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3) and eukaryotes (Class 4). The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively. The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases. These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.

Establishment of a genome-wide RNAi screen; Identification of novel genes involved in clonal maintenance of ALL

2014 ◽  
Vol 226 (03) ◽  
Author(s):  
F Ponthan ◽  
D Pal ◽  
J Vormoor ◽  
O Heidenreich
Keyword(s):  
Rnai Screen ◽  
Novel Genes ◽  
Genome Wide ◽  
A Genome
Sign in / Sign up

Export Citation Format

Share Document