scholarly journals Incomplete MyoD-induced transdifferentiation is associated with chromatin remodeling deficiencies

2017 ◽  
Author(s):  
Dinesh Manandhar ◽  
Lingyun Song ◽  
Ami Kabadi ◽  
Jennifer Kwon ◽  
Lee Edsall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Remodeling ◽  
Global Gene Expression ◽  
Chromatin Accessibility ◽  
Marker Genes ◽  
Target Cells ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Quantitative Analyses

Our current understanding of cellular transdifferentiation systems is limited. It is oftentimes unknown, at a genome-wide scale, how much transdifferentiated cells differ quantitatively from both the starting cells and the target cells. Focusing on transdifferentiation of primary human skin fibroblasts by forced expression of myogenic transcription factor MyoD, we performed quantitative analyses of gene expression and chromatin accessibility profiles of transdifferentiated cells compared to fibroblasts and myoblasts. In this system, we find that while many of the early muscle marker genes are reprogrammed, global gene expression and accessibility changes are still incomplete when compared to myoblasts. In addition, we find evidence of epigenetic memory in the transdifferentiated cells, with reminiscent features of fibroblasts being visible both in chromatin accessibility and gene expression. Quantitative analyses revealed a continuum of changes in chromatin accessibility induced by MyoD, and a strong correlation between chromatin-remodeling deficiencies and incomplete gene expression reprogramming. Classification analyses identified genetic and epigenetic features that distinguish reprogrammed from non-reprogrammed sites, and suggested ways to potentially improve transdifferentiation efficiency. Our approach for combining gene expression, DNA accessibility, and protein-DNA binding data to quantify and characterize the efficiency of cellular transdifferentiation on a genome-wide scale can be applied to any transdifferentiation system.

scholarly journals Study strategies for long non-coding RNAs and their roles in regulating gene expression

2015 ◽  
Vol 20 (2) ◽  
Author(s):  
Dan Qin ◽  
Cunshuan Xu
Keyword(s):  
Gene Expression ◽  
Regulatory Network ◽  
Experimental Methods ◽  
Study Strategies ◽  
Mechanisms Of Action ◽  
Cellular Processes ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Non Coding Rnas

AbstractLong non-coding RNAs (lncRNAs) have attracted considerable attention recently due to their involvement in numerous key cellular processes and in the development of various disorders. New high-throughput methods enable their study on a genome-wide scale. Numerous lncRNAs have been identified and characterized as important members of the biological regulatory network, with significant roles in regulating gene expression at the epigenetic, transcriptional and post-transcriptional levels. This paper summarizes the diverse mechanisms of action of these lncRNAs and looks at the study strategies in this field. A major challenge in future study is to establish more effective bioinformatics and experimental methods to explore the functions, detailed mechanisms of action and structures deciding the functional diversity of lncRNAs, since the vast majority remain unresolved.

scholarly journals Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1606
Author(s):  
Shuai Zhang ◽  
Ruixue Wang ◽  
Cheng Huang ◽  
Ludan Zhang ◽  
Lin Sun
Keyword(s):  
Gene Expression ◽  
Sex Chromosome ◽  
Global Gene Expression ◽  
Regulatory Genes ◽  
Dosage Effect ◽  
Macromolecular Complex ◽  
Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Modulation Of Gene Expression

Aneuploidy, which disrupts the genetic balance due to partial genome dosage changes, is usually more detrimental than euploidy variation. To investigate the modulation of gene expression in aneuploidy, we analyzed the transcriptome sequencing data of autosomal and sex chromosome trisomy in Drosophila. The results showed that most genes on the varied chromosome (cis) present dosage compensation, while the remainder of the genome (trans) produce widespread inverse dosage effects. Some altered functions and pathways were identified as the common characteristics of aneuploidy, and several possible regulatory genes were screened for an inverse dosage effect. Furthermore, we demonstrated that dosage changes of inverse regulator Inr-a/pcf11 can produce a genome-wide inverse dosage effect. All these findings suggest that the mechanism of genomic imbalance is related to the changes in the stoichiometric relationships of macromolecular complex members that affect the overall function. These studies may deepen the understanding of gene expression regulatory mechanisms.

scholarly journals A genome-wide transcriptional analysis of morphology determination inCandida albicans

2013 ◽  
Vol 24 (3) ◽  
pp. 246-260 ◽  
Author(s):  
Patricia L. Carlisle ◽  
David Kadosh
Keyword(s):  
Gene Expression ◽  
Fungal Infections ◽  
Transcriptional Profiling ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Transcriptional Analysis ◽  
Specific Gene ◽  
Genome Wide ◽  
A Genome ◽  
Genetically Manipulated

Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship among global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated with hyphae and are generally expressed at lower levels. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition involves not only down-regulation of known hyphal-specific, genes but also differential expression of additional genes that have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide expression patterns important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.

scholarly journals DNA microarrays, a novel approach in studies of chromatin structure.

2004 ◽  
Vol 51 (1) ◽  
pp. 1-8
Author(s):  
Piotr Widłak
Keyword(s):  
Gene Expression ◽  
Dna Microarray ◽  
Chromatin Structure ◽  
Expression Profiling ◽  
Genetic Information ◽  
Dna Microarrays ◽  
Microarray Technology ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale

The DNA microarray technology delivers an experimental tool that allows surveying expression of genetic information on a genome-wide scale at the level of single genes--for the new field termed functional genomics. Gene expression profiling--the primary application of DNA microarrays technology--generates monumental amounts of information concerning the functioning of genes, cells and organisms. However, the expression of genetic information is regulated by a number of factors that cannot be directly targeted by standard gene expression profiling. The genetic material of eukaryotic cells is packed into chromatin which provides the compaction and organization of DNA for replication, repair and recombination processes, and is the major epigenetic factor determining the expression of genetic information. Genomic DNA can be methylated and this modification modulates interactions with proteins which change the functional status of genes. Both chromatin structure and transcriptional activity are affected by the processes of replication, recombination and repair. Modified DNA microarray technology could be applied to genome-wide study of epigenetic factors and processes that modulate the expression of genetic information. Attempts to use DNA microarrays in studies of chromatin packing state, chromatin/DNA-binding protein distribution and DNA methylation pattern on a genome-wide scale are briefly reviewed in this paper.

scholarly journals H3K4me3 is neither instructive for, nor informed by, transcription

2019 ◽  
Author(s):  
Struan C Murray ◽  
Philipp Lorenz ◽  
Françoise S Howe ◽  
Meredith Wouters ◽  
Thomas Brown ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Environmental Changes ◽  
Expression Patterns ◽  
Gene Activity ◽  
Protein Levels ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Cell Variation

AbstractH3K4me3 is a near-universal histone modification found predominantly at the 5’ region of genes, with a well-documented association with gene activity. H3K4me3 has been ascribed roles as both an instructor of gene expression and also a downstream consequence of expression, yet neither has been convincingly proven on a genome-wide scale. Here we test these relationships using a combination of bioinformatics, modelling and experimental data from budding yeast in which the levels of H3K4me3 have been massively ablated. We find that loss of H3K4me3 has no effect on the levels of nascent transcription or transcript in the population. Moreover, we observe no change in the rates of transcription initiation, elongation, mRNA export or turnover, or in protein levels, or cell-to-cell variation of mRNA. Loss of H3K4me3 also has no effect on the large changes in gene expression patterns that follow galactose induction. Conversely, loss of RNA polymerase from the nucleus has no effect on the pattern of H3K4me3 deposition and little effect on its levels, despite much larger changes to other chromatin features. Furthermore, large genome-wide changes in transcription, both in response to environmental stress and during metabolic cycling, are not accompanied by corresponding changes in H3K4me3. Thus, despite the correlation between H3K4me3 and gene activity, neither appear to be necessary to maintain levels of the other, nor to influence their changes in response to environmental stimuli. When we compare gene classes with very different levels of H3K4me3 but highly similar transcription levels we find that H3K4me3-marked genes are those whose expression is unresponsive to environmental changes, and that their histones are less acetylated and dynamically turned-over. Constitutive genes are generally well-expressed, which may alone explain the correlation between H3K4me3 and gene expression, while the biological role of H3K4me3 may have more to do with this distinction in gene class.

scholarly journals Regulation of global transcription inE. coliby Rsd and 6S RNA

2016 ◽  
Author(s):  
Avantika Lal ◽  
Sandeep Krishna ◽  
Aswin Sai Narain Seshasayee
Keyword(s):  
Rna Polymerase ◽  
Sigma Factor ◽  
Global Gene Expression ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome ◽  
6S Rna ◽  
Wide Scale ◽  
Five Phases ◽  
First Time

ABSTRACTInEscherichia coli, the sigma factor σ70directs RNA polymerase to transcribe growth-related genes, while σ38directs transcription of stress response genes during stationary phase. Two molecules hypothesized to regulate RNA polymerase are the protein Rsd, which binds to σ70, and the non-coding 6S RNA which binds to the RNA polymerase- σ70holoenzyme. Despite multiple studies, the functions of Rsd and 6S RNA remain controversial. Here we use RNA-Seq in five phases of growth to elucidate their function on a genome-wide scale. We show for the first time that Rsd and 6S RNA facilitate σ38activity throughout bacterial growth, while 6S RNA also regulates widely different genes depending upon growth phase. We discover novel interactions between 6S RNA and Rsd and show widespread expression changes in a strain lacking both regulators. Finally, we present a mathematical model of transcription which highlights the crosstalk between Rsd and 6S RNA as a crucial factor in controlling sigma factor competition and global gene expression.

scholarly journals Large-Scale Gene Expression Data Analysis: A New Challenge to Computational Biologists

1999 ◽  
Vol 9 (8) ◽  
pp. 681-688 ◽  
Author(s):  
Michael Q. Zhang
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Large Scale ◽  
Yeast Genome ◽  
Expression Data ◽  
Dna Arrays ◽  
Gene Expression Data Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale

The use of high-density DNA arrays to monitor gene expression at a genome-wide scale constitutes a fundamental advance in biology. In particular, the expression pattern of all genes in Saccharomyces cerevisiae can be interrogated using microarray analysis where cDNAs are hybridized to an array of each of the ∼6000 genes in the yeast genome. In this survey I review three recent experiments related to transcriptional regulation and discuss the great challenge for computational biologists trying to extract functional information from such large-scale gene expression data.

scholarly journals The conserved elongation factor Spn1 is required for normal transcription, histone modifications, and splicing in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Natalia I. Reim ◽  
James Chuang ◽  
Dhawal Jain ◽  
Burak H. Alver ◽  
Peter J. Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Elongation Factor ◽  
Mrna Levels ◽  
Chromatin Dynamics ◽  
Binding Partner ◽  
Genome Wide ◽  
A Genome ◽  
Highly Expressed Genes ◽  
Wide Scale

Spn1/Iws1 is a conserved protein involved in transcription and chromatin dynamics, yet its general in vivo requirement for these functions is unknown. Using a Spn1 depletion system in S. cerevisiae, we demonstrate that Spn1 broadly influences several aspects of gene expression on a genome-wide scale. We show that Spn1 is globally required for normal mRNA levels and for normal splicing of ribosomal protein transcripts. Furthermore, Spn1 maintains the localization of H3K36 and H3K4 methylation across the genome and is required for normal histone levels at highly expressed genes. Finally, we show that the association of Spn1 with the transcription machinery is strongly dependent on its binding partner, Spt6, while the association of Spt6 and Set2 with transcribed regions is partially dependent on Spn1. Taken together, our results show that Spn1 affects multiple aspects of gene expression and provide additional evidence that it functions as a histone chaperone in vivo.

I. Global gene expression profiling using DNA microarrays

2002 ◽  
Vol 282 (3) ◽  
pp. G397-G402 ◽  
Author(s):  
Mayi Arcellana-Panlilio ◽  
Stephen M. Robbins
Keyword(s):  
Dna Microarrays ◽  
Genomic Sequence ◽  
Structural Information ◽  
Global Gene Expression ◽  
Factors Affecting ◽  
Genome Wide ◽  
Specific Hybridization ◽  
A Genome ◽  
Global Gene Expression Profiling ◽  
Wide Scale

Having the complete human genomic sequence poses a new challenge: to use genomic structural information to display and analyze biological processes on a genome-wide scale to assign gene function. DNA microarrays are a miniaturized, ordered arrangement of nucleic acid fragments from individual genes located at defined positions on a solid support, enabling the analysis of thousands of genes in parallel by specific hybridization. This review describes technical aspects, discusses relevant applications, and suggests factors affecting the use of this technology and how it fits in the grand scheme of meeting the needs of the postgenomic era.

scholarly journals The conserved elongation factor Spn1 is required for normal transcription, histone modifications, and splicing in Saccharomyces cerevisiae

2020 ◽  
Vol 48 (18) ◽  
pp. 10241-10258 ◽  
Author(s):  
Natalia I Reim ◽  
James Chuang ◽  
Dhawal Jain ◽  
Burak H Alver ◽  
Peter J Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Elongation Factor ◽  
Mrna Levels ◽  
Chromatin Dynamics ◽  
Genome Wide ◽  
A Genome ◽  
Highly Expressed Genes ◽  
Wide Scale

Abstract Spn1/Iws1 is a conserved protein involved in transcription and chromatin dynamics, yet its general in vivo requirement for these functions is unknown. Using a Spn1 depletion system in Saccharomyces cerevisiae, we demonstrate that Spn1 broadly influences several aspects of gene expression on a genome-wide scale. We show that Spn1 is globally required for normal mRNA levels and for normal splicing of ribosomal protein transcripts. Furthermore, Spn1 maintains the localization of H3K36 and H3K4 methylation across the genome and is required for normal histone levels at highly expressed genes. Finally, we show that the association of Spn1 with the transcription machinery is strongly dependent on its binding partner, Spt6, while the association of Spt6 and Set2 with transcribed regions is partially dependent on Spn1. Taken together, our results show that Spn1 affects multiple aspects of gene expression and provide additional evidence that it functions as a histone chaperone in vivo.

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