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

2004 ◽  
Vol 51 (1) ◽  
pp. 1-8
Author(s):  
Piotr Widłak

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.

2011 ◽  
Vol 43 (3) ◽  
pp. 148-160 ◽  
Author(s):  
Stefania M. C. Simeone ◽  
Melissa W. Li ◽  
Pierre Paradis ◽  
Ernesto L. Schiffrin

Endothelin (ET)-1 plays an important pathophysiological role in several vascular diseases including hypertension and atherosclerosis. Transgenic mice overexpressing human preproET-1 selectively in the endothelium (eET-1) exhibit vascular injury in the absence of blood pressure elevation. ET-1 overexpression may induce vascular injury by inducing changes in gene expression. To understand mechanisms whereby ET-1 induces vascular damage, vascular gene expression profiling was performed using DNA microarrays. RNA from mesenteric arteries of male and female young (6–7 wk) and mature (6–8 mo) eET-1 and wild-type (WT) mice was isolated, and changes in gene expression were determined by genome-wide expression profiling using Illumina microarray and FlexArray software. Data were analyzed using a relaxed and a stringent statistical approach. The gene lists were compared and analyzed as well with Ingenuity Pathway Analysis. The most common change was an increase in the expression of lipid metabolism genes. Four of these genes were validated by qPCR, cyp51, dgat2, and scd1 genes in young and elovl6 in both young and mature male mice, supporting a role of ET-1 in atherosclerosis. To test the hypothesis that ET-1 participates in mechanisms leading to atherosclerosis, we crossed eET-1 with atherosclerosis-prone apoE−/− mice to determine whether ET-1 overexpression exacerbates high-fat diet (HFD)-induced atherosclerosis using oil red O staining of descending thoracic aorta. HFD increased lipid plaques by 3-, 27-, and 86-fold in eET-1, apoE−/−, and crossed mice, respectively, vs. WT. This suggests that increased endothelial ET-1 expression results in early changes in gene expression in the vascular wall that enhance lipid biosynthesis and accelerate progression of atherosclerosis.


2015 ◽  
Vol 20 (2) ◽  
Author(s):  
Dan Qin ◽  
Cunshuan Xu

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.


Author(s):  
Peter B. Vermeulen ◽  
Gert Van den Eynden ◽  
Pascal Finetti ◽  
Daniel Birnbaum ◽  
Naoto T. Ueno ◽  
...  

2019 ◽  
Author(s):  
Struan C Murray ◽  
Philipp Lorenz ◽  
Françoise S Howe ◽  
Meredith Wouters ◽  
Thomas Brown ◽  
...  

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.


Blood ◽  
2009 ◽  
Vol 113 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Bas J. Wouters ◽  
Bob Löwenberg ◽  
Ruud Delwel

Abstract The past decade has shown a marked increase in the use of high-throughput assays in clinical research into human cancer, including acute myeloid leukemia (AML). In particular, genome-wide gene expression profiling (GEP) using DNA microarrays has been extensively used for improved understanding of the diagnosis, prognosis, and pathobiology of this heterogeneous disease. This review discusses the progress that has been made, places the technologic limitations in perspective, and highlights promising future avenues


1999 ◽  
Vol 9 (8) ◽  
pp. 681-688 ◽  
Author(s):  
Michael Q. Zhang

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.


2017 ◽  
Author(s):  
Dinesh Manandhar ◽  
Lingyun Song ◽  
Ami Kabadi ◽  
Jennifer Kwon ◽  
Lee Edsall ◽  
...  

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.


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