scholarly journals Developmental Methylome of the Medicinal Plant Catharanthus roseus Unravels the Tissue-Specific Control of the Monoterpene Indole Alkaloid Pathway by DNA Methylation

2020 ◽  
Vol 21 (17) ◽  
pp. 6028
Author(s):  
Thomas Dugé de Bernonville ◽  
Stéphane Maury ◽  
Alain Delaunay ◽  
Christian Daviaud ◽  
Cristian Chaparro ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factors ◽  
Catharanthus Roseus ◽  
Wide Spectrum ◽  
Indole Alkaloid ◽  
Specific Gene ◽  
Experimental Conditions ◽  
Tissue Specific ◽  
Plant Parts ◽  
Helix Loop Helix

Catharanthus roseus produces a wide spectrum of monoterpene indole alkaloids (MIAs). MIA biosynthesis requires a tightly coordinated pathway involving more than 30 enzymatic steps that are spatio-temporally and environmentally regulated so that some MIAs specifically accumulate in restricted plant parts. The first regulatory layer involves a complex network of transcription factors from the basic Helix Loop Helix (bHLH) or AP2 families. In the present manuscript, we investigated whether an additional epigenetic layer could control the organ-, developmental- and environmental-specificity of MIA accumulation. We used Whole-Genome Bisulfite Sequencing (WGBS) together with RNA-seq to identify differentially methylated and expressed genes among nine samples reflecting different plant organs and experimental conditions. Tissue specific gene expression was associated with specific methylation signatures depending on cytosine contexts and gene parts. Some genes encoding key enzymatic steps from the MIA pathway were found to be simultaneously differentially expressed and methylated in agreement with the corresponding MIA accumulation. In addition, we found that transcription factors were strikingly concerned by DNA methylation variations. Altogether, our integrative analysis supports an epigenetic regulation of specialized metabolisms in plants and more likely targeting transcription factors which in turn may control the expression of enzyme-encoding genes.

scholarly journals Transcriptomic Analysis and Specific Expression of Transcription Factor Genes in the Root and Sporophyll of Dryopteris fragrans (L.) Schott

2020 ◽  
Vol 21 (19) ◽  
pp. 7296
Author(s):  
Lingling Chen ◽  
Dongrui Zhang ◽  
Chunhua Song ◽  
Hemeng Wang ◽  
Xun Tang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Glandular Trichomes ◽  
Transcriptomic Analysis ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Transcription Factor Genes ◽  
Dryopteris Fragrans ◽  
Different Tissues

Background: Dryopteris fragrans, which is densely covered with glandular trichomes, is considered to be one of the ferns with the most medicinal potential. The transcriptomes from selected tissues of D. fragrans were collected and analyzed for functional and comparative genomic studies. The aim of this study was to determine the transcriptomic characteristics of wild D. fragrans sporangium in tissues from the SR (root), SL (sporophyll), and TRL (sporophyll with glandular trichomes removed). Results: Cluster analysis identified genes that were highly expressed in an organ-specific manner according to read mapping, feature counting, and normalization. The functional map identified gene clusters that can uniquely describe the function of each tissue. We identified a group of three tissue-specific transcription factors targeting the SL, SR, and TRL. In addition, highly expressed transcription factors (TFs) were found in each tissue-specific gene cluster, where ERF and bHLH transcription factors were the two types showing the most distinct expression patterns between the three different tissues. The specific expression of transcription factor genes varied between the different types of tissues. The numbers of transcription factors specifically expressed in the roots and sporophylls were 60 and 30, respectively, while only seven were found for the sporophylls with glandular trichomes removed. The expression of genes known to be associated with the development of glandular trichomes in flowering plants, including MIXTA, ATML1, and MYB106, were also validated and are discussed. In particular, a unigene encoding MIXTA was identified and exhibited the highest expression level in SL in D. fragrans. Conclusions: This study is the first report of global transcriptomic analysis in different tissues of D. fragrans, and the first to discuss these findings in the context of the development of homologous glandular trichomes. These results set the stage for further research on the development, stress resistance, and secondary metabolism of D. fragrans glandular trichomes.

scholarly journals Methylation of an ETS site in the intron enhancer of the keratin 18 gene participates in tissue-specific repression.

1997 ◽  
Vol 17 (9) ◽  
pp. 4885-4894 ◽  
Author(s):  
A Umezawa ◽  
H Yamamoto ◽  
K Rhodes ◽  
M J Klemsz ◽  
R A Maki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factors ◽  
Transgenic Mice ◽  
Binding Site ◽  
Binding Sites ◽  
Epigenetic Modification ◽  
Ets Transcription Factors ◽  
Tissue Specific ◽  
Mouse Tissues ◽  
Keratin 18

The activities of ETS transcription factors are modulated by posttranscriptional modifications and cooperation with other proteins. Another factor which could alter the regulation of genes by ETS transcription factors is DNA methylation of their cognate binding sites. The optimal activity of the keratin 18 (K18) gene is dependent upon an ETS binding site within an enhancer region located in the first intron. The methylation of the ETS binding site was correlated with the repression of the K18 gene in normal human tissues and in K18 transgenic mouse tissues. Neither recombinant ETS2 nor endogenous spleen ETS binding activities bound the methylated site effectively. Increased expression of the K18 gene in spleens of transgenic mice by use of an alternative, cryptic promoter 700 bp upstream of the enhancer resulted in modestly decreased methylation of the K18 ETS site and increased RNA expression. Expression in transgenic mice of a mutant K18 gene, which was still capable of activation by ETS factors but was no longer a substrate for DNA methylation of the ETS site, was fivefold higher in spleen and heart. However, expression in other organs such as liver and intestine was similar to that of the wild-type gene. This result suggests that DNA methylation of the K18 ETS site may be functionally important in the tissue-specific repression of the K18 gene. Epigenetic modification of the binding sites for some ETS transcription factors may result in a refractory transcriptional response even in the presence of necessary trans-acting activities.

scholarly journals The Developmental Control of Osteoblast-Specific Gene Expression: Role of Specific Transcription Factors and the Extracellular Matrix Environment

1999 ◽  
Vol 10 (1) ◽  
pp. 40-57 ◽  
Author(s):  
R.T. Franceschi
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Developmental Process ◽  
Positional Information ◽  
Cleidocranial Dysplasia ◽  
Specific Gene ◽  
Tissue Specific ◽  
Specific Gene Expression ◽  
Specific Differentiation

Bone formation is a carefully controlled developmental process involving morphogen-mediated patterning signals that define areas of initial mesenchyme condensation followed by induction of cell-specific differentiation programs to produce chondrocytes and osteoblasts. Positional information is conveyed via gradients of molecules, such as Sonic Hedgehog that are released from cells within a particular morphogenic field together with region-specific patterns of hox gene expression. These, in turn, regulate the localized production of bone morphogenetic proteins and related molecules which initiate chondrocyte- and osteoblast-specific differentiation programs. Differentiation requires the initial commitment of mesenchymal stem cells to a given lineage, followed by induction of tissue-specific patterns of gene expression. Considerable information about the control of osteoblast-specific gene expression has come from analysis of the promoter regions of genes encoding proteins like osteocalcin that are selectively expressed in bone. Both general and tissue-specific transcription factors control this promoter. Osf2/Cbfal, the first osteoblast-specific transcription factor to be identified, is expressed early in the osteoblast lineage and interacts with specific DNA sequences in the osteocalcin promoter essential for its selective expression in osteoblasts. The OSF2/CBFA1 gene is necessary for the development of mineralized tissues, and its mutation causes the human disease, cleidocranial dysplasia. Committed osteoprogenitor cells already expressing Osf2/Cbfa1 must synthesize a collagenous ECM before they will differentiate. A ceII:ECM interaction mediated by integrin-type cell-surface receptors is essential for the induction of osteocalcin and other osteoblast-related proteins. This interaction stimulates the binding of Osf2/Cbfa 1 to the osteocalcin promoter through an as-yet-undefined mechanism.

scholarly journals Gene-Specific Methylation Profiles for Integrative Methylation-Expression Analysis in Cancer Research

2019 ◽  
Author(s):  
Yusha Liu ◽  
Keith A. Baggerly ◽  
Elias Orouji ◽  
Ganiraju Manyam ◽  
Huiqin Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Penalized Regression ◽  
Tissue Type ◽  
Specific Gene ◽  
Integrative Genomics ◽  
Tissue Specific ◽  
Cancer Subtypes ◽  
Shiny App ◽  
Gene Level

AbstractDNA methylation is a key epigenetic factor regulating gene expression. While promoter-associated methylation has been extensively studied, recent publications have revealed that functionally important methylation also occurs in intergenic and distal regions, and varies across genes and tissue types. Given the growing importance of inter-platform integrative genomic analyses, there is an urgent need to develop methods to construct gene-level methylation summaries that account for the potentially complex relationships between methylation and expression. We introduce a novel sequential penalized regression approach to construct gene-specific methylation profiles (GSMPs) which find for each gene and tissue type a sparse set of CpGs best explaining gene expression and weights indicating direction and strength of association. Using TCGA and MD Anderson colorectal cohorts to build and validate our models, we demonstrate our strategy better explains expression variability than standard approaches and produces gene-level scores showing key methylation differences across recently discovered colorectal cancer subtypes. We share an R Shiny app that presents GSMP results for colorectal, breast, and pancreatic cancer with plans to extend it to all TCGA cancer types. Our approach yields tissue-specific, gene-specific sparse lists of functionally important CpGs that can be used to construct gene-level methylation scores that are maximally correlated with gene expression for use in integrative models, and produce a tissue-specific summary of which genes appear to be strongly regulated by methylation. Our results introduce an important resource to the biomedical community for integrative genomics analyses involving DNA methylation.

scholarly journals Hypermethylation of human DNA: Fine-tuning transcription associated with development

2017 ◽  
Author(s):  
Carl Baribault ◽  
Kenneth C. Ehrlich ◽  
V. K. Chaithanya Ponnaluri ◽  
Sriharsa Pradhan ◽  
Michelle Lacey ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Regulatory Elements ◽  
Fine Tuning ◽  
Ctcf Binding ◽  
Specific Gene ◽  
Dna Hypermethylation ◽  
Specific Expression ◽  
Lncrna Gene ◽  
Tissue Specific ◽  
Tissue Specific Expression

AbstractTissue-specific gene transcription can be affected by DNA methylation in ways that are difficult to discern from studies focused on genome-wide analyses of differentially methylated regions (DMRs). We studied 95 genes in detail using available epigenetic and transcription databases to detect and elucidate less obvious associations between development-linked hypermethylated DMRs in myoblasts (Mb) and cell-and tissue-specific expression. Many of these genes encode developmental transcription factors and display DNA hypermethylation also in skeletal muscle (SkM) and a few heterologous samples (e.g., aorta, mammary epithelial cells, or brain) among the 38 types of human cell cultures or tissues examined. Most of the DMRs overlapped transcription regulatory elements, including canonical, alternative, or cryptic promoters; enhancers; CTCF binding sites; and long-noncoding RNA (lncRNA) gene regions. Among the prominent relationships between DMRs and expression was promoter-region hypermethylation accompanying repression in Mb but not in many other repressed samples (26 genes). Another surprising relationship was down-modulated (but not silenced) expression in Mb associated with DNA hypermethylation at cryptic enhancers in Mb although such methylation was absent in both non-expressing samples and highly expressing samples (24 genes). The tissue-specificity of DNA hypermethylation can be explained for many of the genes by their roles in prenatal development or by the tissue-specific expression of neighboring genes. Besides elucidating developmental epigenetics, our study provides insights into the roles of abnormal DNA methylation in disease, e.g., cancer, Duchenne muscular dystrophy, and congenital heart malformations.

scholarly journals CG methylation covaries with differential gene expression between leaf and floral bud tissues of Brachypodium distachyon

2015 ◽  
Author(s):  
Kyria Roessler ◽  
Shohei Takuno ◽  
Brandon Gaut
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Sequence Data ◽  
Brachypodium Distachyon ◽  
Grass Species ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Model Grass ◽  
Floral Bud

DNA methylation has the potential to influence plant growth and development through its influence on gene expression. To date, however, the evidence from plant systems is mixed as to whether patterns of DNA methylation vary significantly among tissues and, if so, whether these differences affect tissue-specific gene expression. To address these questions, we analyzed both bisulfite sequence (BSseq) and transcriptomic sequence data from three biological replicates of two tissues (leaf and floral bud) from the model grass species Brachypodium distachyon. Our first goal was to determine whether tissues were more differentiated in DNA methylation than explained by variation among biological replicates. Tissues were more differentiated than biological replicates, but the analysis of replicated data revealed high (>50%) false positive rates for the inference of differentially methylated sites (DMSs) and differentially methylated regions (DMRs). Comparing methylation to gene expression, we found that differential CG methylation consistently covaried negatively with gene expression, regardless as to whether methylation was within genes, within their promoters or even within their closest transposable element. The relationship between gene expression and either CHG or CHH methylation was less consistent. In total, CG methylation in promoters explained 9% of the variation in tissue-specific expression across genes, suggesting that CG methylation is a minor but appreciable factor in tissue differentiation.

Epigenetics of Cellular Memory: Insights from the Chromatin Accessibility Landscape of the Mitotic Genome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4342-4342
Author(s):  
Chris C.S. Hsiung ◽  
Christapher Morrissey ◽  
Maheshi Udugama ◽  
Christopher Frank ◽  
Cheryl A. Keller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factors ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Dnase I ◽  
Specific Gene ◽  
Tissue Specific ◽  
Dnase I Sensitivity ◽  
Mitotic Chromatin

Abstract Normal development requires the coordination of cell cycle progression and gene expression to produce physiologically appropriate cell numbers of various lineages. The concomitant dysregulation of these two cellular programs is central to many malignant and non-malignant hematologic diseases, yet researchers still lack clear, general principles of how intrinsic properties of cell division could influence transcriptional regulation. Mitosis is a unique phase of the cell cycle that dramatically disrupts transcription: chromosomes condense to form microscopically recognizable structures, the nucleus is disassembled, RNA synthesis ceases, and the transcription machinery and many transcription factors are evicted from mitotic chromatin. How cells “remember” tissue-specific transcriptional programs through mitotic divisions remains largely unknown. Some transcription factors, including the erythroid master regulator, GATA1, and certain chromatin features are known to remain associated with DNA during mitosis. These molecular entities have been proposed to serve as mitotic “bookmarks” -- molecules that store gene regulatory information at individual loci through mitosis. However, we have limited knowledge of the composition, mechanism and function of mitotic bookmarks. In this context, chromatin structure deserves special consideration, as chromosome condensation during mitosis could potentially hinder transcription factor binding. To obtain the first genome-wide view of chromatin accessibility during mitosis, we mapped the DNase I sensitivity of the interphase versus mitotic genome in two maturation stages in a murine erythroblast cell line, G1E. Despite microscopic condensation of chromosomes during mitosis, we found that DNase I sensitivity is extensively preserved throughout the mappable genome, indicating that mitotic chromatin is not as condensed as commonly presumed. Individual genes and cis-regulatory elements can maintain all, part of, or none of its interphase accessibility during mitosis, demonstrating that accessibility of mitotic chromatin is locally specified. Promoters generally maintain accessibility during mitosis; moreover, promoters with the highest degree of accessibility preservation in mitosis in G1E cells tend to also be accessible across many murine tissues in interphase. In contrast to promoters, we found that enhancer accessibility is preferentially lost during mitosis, raising the possibility that memory of enhancer regulation may be altered during mitosis. Since enhancers play crucial roles in specifying tissue-specific gene expression patterns, we propose that this phase of the cell cycle may be especially susceptible to resetting of transcriptional programs. This hypothesis is supported by our preliminary results that revealed aberrant RNA polymerase II re-engagement with the genome and transcript production in early G1. Thus, mitosis could be a source of gene expression heterogeneity, with potential implications for cell fate transitions in proliferative cells, such as during stem cell lineage commitment, experimental reprogramming, and tumorigenesis. Disclosures No relevant conflicts of interest to declare.

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