scholarly journals Synchronization of stochastic expressions drives the clustering of functionally related genes

2019 ◽  
Vol 5 (10) ◽  
pp. eaax6525 ◽  
Author(s):  
Haiqing Xu ◽  
Jing-Jing Liu ◽  
Zhen Liu ◽  
Ying Li ◽  
Yong-Su Jin ◽  
...  
Keyword(s):  
Biological Significance ◽  
Expression Ratio ◽  
Chromatin Dynamics ◽  
Gene Expression Noise ◽  
Consecutive Reactions ◽  
Manipulative Experiments ◽  
Genes Encoding ◽  
Stochastic Expression ◽  
Widespread Phenomenon ◽  
Eukaryotic Genomes

Functionally related genes tend to be chromosomally clustered in eukaryotic genomes even after the exclusion of tandem duplicates, but the biological significance of this widespread phenomenon is unclear. We propose that stochastic expression fluctuations of neighboring genes resulting from chromatin dynamics are more or less synchronized such that their expression ratio is more stable than that for unlinked genes. Consequently, chromosomal clustering could be advantageous when the expression ratio of the clustered genes needs to stay constant, for example, because of the accumulation of toxic compounds when this ratio is altered. Evidence from manipulative experiments on the yeast GAL cluster, comprising three chromosomally adjacent genes encoding enzymes catalyzing consecutive reactions in galactose catabolism, unequivocally supports this hypothesis and elucidates how disorder in one biological phenomenon—gene expression noise—could prompt the emergence of order in another—genome organization.

scholarly journals Chromosome-wide co-fluctuation of stochastic gene expression in mammalian cells

2019 ◽  
Author(s):  
Mengyi Sun ◽  
Jianzhi Zhang
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Three Dimensional ◽  
Sequencing Data ◽  
Chromatin Dynamics ◽  
Gene Expression Noise ◽  
Genes Encoding ◽  
The Face ◽  
Allele Specific ◽  
Genomic Scale

ABSTRACTGene expression is subject to stochastic noise, but to what extent and by which means such stochastic variations are coordinated among different genes are unclear. We hypothesize that neighboring genes on the same chromosome co-fluctuate in expression because of their common chromatin dynamics, and verify it at the genomic scale using allele-specific single-cell RNA-sequencing data of mouse cells. Unexpectedly, the co-fluctuation extends to genes that are over 60 million bases apart. We provide evidence that this long-range effect arises in part from chromatin co-accessibilities of linked loci attributable to three-dimensional proximity, which is much closer intra-chromosomally than inter-chromosomally. We further show that genes encoding components of the same protein complex tend to be chromosomally linked, likely resulting from natural selection for intracellular among-component dosage balance. These findings have implications for both the evolution of genome organization and optimal design of synthetic genomes in the face of gene expression noise.

A novel nucleolar G-protein conserved in eukaryotes

2001 ◽  
Vol 114 (1) ◽  
pp. 173-185 ◽  
Author(s):  
J.H. Park ◽  
B.C. Jensen ◽  
C.T. Kifer ◽  
M. Parsons
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Biological Significance ◽  
Binding Region ◽  
Founding Member ◽  
Nucleolar Proteins ◽  
Evolutionarily Conserved ◽  
Genes Encoding ◽  
Sequence Characteristics ◽  
Two Hybrid

We describe here a novel, evolutionarily conserved set of predicted G-proteins. The founding member of this family, TbNOG1, was identified in a two-hybrid screen as a protein that interacts with NOPP44/46, a nucleolar phosphoprotein of Trypanosoma brucei. The biological relevance of the interaction was verified by co-localization and co-immunoprecipitation. TbNOG1 localized to the trypanosome nucleolus and interacted with domains of NOPP44/46 that are found in several other nucleolar proteins. Genes encoding proteins highly related to TbNOG1 are present in yeast and metazoa, and related G domains are found in bacteria. We show that NOG1 proteins in humans and Saccharomyces cerevisae are also nucleolar. The S. cerevisae NOG1 gene is essential for cell viability, and mutations in the predicted G motifs abrogate function. Together these data suggest that NOG1 may play an important role in nucleolar functions. The GTP-binding region of TbNOG1 is similar to those of Obg and DRG proteins, which, together with NOG, form a newly recognized family of G-proteins, herein named ODN. The ODN family differs significantly from other G-protein families, and shows several diagnostic sequence characteristics. All organisms appear to possess an ODN gene, pointing to the biological significance of this family of G-proteins.

scholarly journals DNA repair mechanisms and gametogenesis

Reproduction ◽  
2001 ◽  
pp. 31-39 ◽  
Author(s):  
WM Baarends ◽  
R van der Laan ◽  
JA Grootegoed
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Gene Knockout ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Chromatin Dynamics ◽  
Dna Mismatch ◽  
Dna Repair Mechanisms ◽  
Genes Encoding ◽  
Repair Mechanisms

In mammals, there is a complex and intriguing relationship between DNA repair and gametogenesis. DNA repair mechanisms are involved not only in the repair of different types of DNA damage in developing germline cells, but also take part in the meiotic recombination process. Furthermore, the DNA repair mechanisms should tolerate mutations occurring during gametogenesis, to a limited extent. In the present review, several gametogenic aspects of DNA mismatch repair, homologous recombination repair and postreplication repair are discussed. In addition, the role of DNA damage-induced cell cycle checkpoint control is considered briefly. It appears that many genes encoding proteins that take part in DNA repair mechanisms show enhanced or specialized expression during mammalian gametogenesis, and several gene knockout mouse models show male or female infertility. On the basis of such knowledge and models, future experiments may provide more information about the precise relationship between DNA repair, chromatin dynamics, and genomic stability versus instability during gametogenesis.

scholarly journals A forty-year journey in plant research: original contributions to flavonoid biochemistry

2005 ◽  
Vol 83 (5) ◽  
pp. 433-450 ◽  
Author(s):  
Ragai K Ibrahim
Keyword(s):  
Three Dimensional ◽  
Biological Significance ◽  
Flavonoid Biosynthesis ◽  
Dimensional Structure ◽  
Enzymatic Reactions ◽  
Research Career ◽  
Substrate Preferences ◽  
Genes Encoding ◽  
The Common ◽  
New Compounds

This review highlights original contributions by the author to the field of flavonoid biochemistry during his research career of more than four decades. These include elucidation of novel aspects of some of the common enzymatic reactions involved in the later steps of flavonoid biosynthesis, with emphasis on methyltransferases, glucosyltransferases, sulfotransferases, and an oxoglutarate-dependent dioxygenase, as well as cloning, and inferences about phylogenetic relationships, of the genes encoding some of these enzymes. The three-dimensional structure of a flavonol O-methyltransferase was studied through homology-based modeling, using a caffeic acid O-methyltransferase as a template, to explain their strict substrate preferences. In addition, the biological significance of enzymatic prenylation of isoflavones, as well as their role as phytoanticipins and inducers of nodulation genes, are emphasized. Finally, the potential application of knowledge about the genes encoding these enzyme reactions is discussed in terms of improving plant productivity and survival, modification of flavonoid profiles, and the search for new compounds with pharmaceutical and (or) nutraceutical value.Key words: flavonoid enzymology, metabolite localization, gene cloning, 3-D structure, phylogeny.

Dispersed Repetitive Sequences in Eukaryotic Genomes and Their Possible Biological Significance

1983 ◽  
Vol 47 (0) ◽  
pp. 1109-1121 ◽  
Author(s):  
G.P. Georgiev ◽  
D.A. Kramerov ◽  
A.P. Ryskov ◽  
K.G. Skryabin ◽  
E.M. Lukanidin
Keyword(s):  
Repetitive Sequences ◽  
Biological Significance ◽  
Eukaryotic Genomes

scholarly journals The impact of chromatin dynamics on Cas9-mediated genome editing in human cells

2016 ◽  
Author(s):  
René M. Daer ◽  
Josh P. Cutts ◽  
David A. Brafman ◽  
Karmella A. Haynes
Keyword(s):  
Genome Editing ◽  
Mammalian Cells ◽  
Underlying Mechanism ◽  
Genomic Locus ◽  
Chromatin Dynamics ◽  
Transgenic Cell ◽  
The Impact ◽  
The Relationship ◽  
Transgenic Cell Line ◽  
Eukaryotic Genomes

ABSTRACTIn order to efficiently edit eukaryotic genomes, it is critical to test the impact of chromatin dynamics on CRISPR/Cas9 function and develop strategies to adapt the system to eukaryotic contexts. So far, research has extensively characterized the relationship between the CRISPR endonuclease Cas9 and the composition of the RNADNA duplex that mediates the system’s precision. Evidence suggests that chromatin modifications and DNA packaging can block eukaryotic genome editing by custom-built DNA endonucleases like Cas9; however, the underlying mechanism of Cas9 inhibition is unclear. Here, we demonstrate that closed, gene-silencing-associated chromatin is a mechanism for the interference of Cas9-mediated DNA editing. Our assays use a transgenic cell line with a drug-inducible switch to control chromatin states (open and closed) at a single genomic locus. We show that closed chromatin inhibits editing at specific target sites, and that artificial reversal of the silenced state restores editing efficiency. These results provide new insights to improve Cas9-mediated editing in human and other mammalian cells.

scholarly journals Dosage sensitivity of X-linked genes in human embryonic single cells

2018 ◽  
Author(s):  
Jian-Rong Yang ◽  
Xiaoshu Chen
Keyword(s):  
Single Cells ◽  
Embryonic Stem ◽  
Housekeeping Genes ◽  
Human Embryos ◽  
Cell Stage ◽  
Expression Ratio ◽  
Gene Expression Noise ◽  
Expression Levels ◽  
Cell Transcriptome ◽  
Dosage Sensitivity

ABSTRACTFifty years ago, Susumu Ohno proposed that the expression levels of X-linked genes have doubled as dosage compensation for autosomal genes due to degeneration of Y-linked homologs during evolution of mammalian sex chromosomes. Recent studies have nevertheless shown that the X to autosome expression ratio equals ~1 in haploid human parthenogenetic embryonic stem (pES) cells and ~0.5 in diploid pES cells, thus refuting Ohno’s hypothesis. Here, by reanalyzing a RNA-seq-based single-cell transcriptome dataset of human embryos (Petropoulos, et al. 2016), we found that from the 8-cell stage until the time-point just prior to implantation, the expression levels of X-linked genes are not two-fold upregulated in male cells and gradually decrease from two-fold in female cells. This observation suggests that the expression levels of X-linked genes are imbalanced, with autosomal genes starting from the early 8-cell stage, and that the dosage conversion is fast, such that the X:AA expression ratio reaches ~0.5 in no more than a week. Additional analyses of gene expression noise further suggest that the dosage sensitivity of X-linked genes is weaker than that of autosomal genes in differentiated female cells, which contradicts a key assumption of Ohno’s hypothesis. Moreover, the dosage-sensitive housekeeping genes are preferentially located on autosomes, implying selection against X-linkage for dosage-sensitive genes. Our results collectively suggest an alternative to Ohno’s hypothesis that X-linked genes are less likely to be dosage sensitive than autosomal genes.

scholarly journals Nα-terminal acetylation of proteins by NatA and NatB serves distinct physiological roles in Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Ulrike A. Friedrich ◽  
Mostafa Zedan ◽  
Bernd Hessling ◽  
Kai Fenzl ◽  
Ludovic Gillet ◽  
...  
Keyword(s):  
Stress Responses ◽  
Ribosomal Proteins ◽  
Protein Modification ◽  
Protein Quality ◽  
Biological Significance ◽  
General Role ◽  
Altered Expression ◽  
Phenotypic Differences ◽  
Genes Encoding

SummaryN-terminal (Nt)-acetylation is a highly prevalent co-translational protein modification in eukaryotes, catalyzed by at least five Nt-acetyltransferases (Nat) with differing specificities. Nt-acetylation has been implicated in protein quality control but its broad biological significance remains elusive. We investigated the roles of the two major Nats of S. cerevisiae, NatA and NatB, by performing transcriptome, translatome and proteome profiling of natAΔ and natBΔ mutants. Our results do not support a general role of Nt-acetylation in protein degradation but reveal an unexpected range of Nat-specific phenotypes. NatA is implicated in systemic adaptation control, as natAΔ mutants display altered expression of transposons, sub-telomeric genes, pheromone response genes and nuclear genes encoding mitochondrial ribosomal proteins. NatB predominantly affects protein folding, as natBΔ mutants accumulate protein aggregates, induce stress responses and display reduced fitness in absence of the ribosome-associated chaperone Ssb. These phenotypic differences indicate that controlling Nat activities may serve to elicit distinct cellular responses.

scholarly journals Evidence that Spt2/Sin1, an HMG-Like Factor, Plays Roles in Transcription Elongation, Chromatin Structure, and Genome Stability in Saccharomyces cerevisiae

2006 ◽  
Vol 26 (4) ◽  
pp. 1496-1509 ◽  
Author(s):  
Amine Nourani ◽  
Francois Robert ◽  
Fred Winston
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genome Stability ◽  
Transcription Elongation ◽  
Coding Region ◽  
Elongation Factors ◽  
Chromatin Dynamics ◽  
Coding Regions ◽  
Genome Wide ◽  
Genes Encoding ◽  
Approaches To Study

ABSTRACT Spt2/Sin1 is a DNA binding protein with HMG-like domains that has been suggested to play a role in chromatin-mediated transcription in Saccharomyces cerevisiae. Previous studies have suggested models in which Spt2 plays an inhibitory role in the initiation of transcription of certain genes. In this work, we have taken several approaches to study Spt2 in greater detail. Our results have identified previously unknown genetic interactions between spt2Δ and mutations in genes encoding transcription elongation factors, including members of the PAF and HIR/HPC complexes. In addition, genome-wide and gene-specific chromatin immunoprecipitation analyses suggest that Spt2 is primarily associated with coding regions in a transcription-dependent fashion. Furthermore, our results show that Spt2, like other elongation factors, is required for the repression of transcription from a cryptic promoter within a coding region and that Spt2 is also required for repression of recombination within transcribed regions. Finally, we provide evidence that Spt2 plays a role in regulating the levels of histone H3 over transcribed regions. Taken together, our results suggest a direct link for Spt2 with transcription elongation, chromatin dynamics, and genome stability.

scholarly journals A stitch in time: Replicate early and escape dosage compensation to express more

2017 ◽  
Vol 216 (7) ◽  
pp. 1869-1870
Author(s):  
María Gómez
Keyword(s):  
Dosage Compensation ◽  
Biological Significance ◽  
Replication Timing ◽  
Expression Levels ◽  
Cell Biol ◽  
Early Replication ◽  
Eukaryotic Genomes

The biological significance of conserved replication timing patterns in eukaryotic genomes remains a mystery. In this issue, Müller and Nieduszynski (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201701061) find that early replication is a requirement for the highest expression levels of certain genes.

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