Sulphur starvation induces the expression of microRNA-395 and one of its target genes but in different cell types

The dorsal ectoderm of the Drosophila embryo is subdivided into different cell types by an activity gradient of two TGF(β) signaling molecules, Decapentaplegic (Dpp) and Screw (Scw). Patterning responses to this gradient depend on a secreted inhibitor, Short gastrulation (Sog) and a newly identified transcriptional repressor, Brinker (Brk), which are expressed in neurogenic regions that abut the dorsal ectoderm. Here we examine the expression of a number of Dpp target genes in transgenic embryos that contain ectopic stripes of Dpp, Sog and Brk expression. These studies suggest that the Dpp/Scw activity gradient directly specifies at least three distinct thresholds of gene expression in the dorsal ectoderm of gastrulating embryos. Brk was found to repress two target genes, tailup and pannier, that exhibit different limits of expression within the dorsal ectoderm. These results suggest that the Sog inhibitor and Brk repressor work in concert to establish sharp dorsolateral limits of gene expression. We also present evidence that the activation of Dpp/Scw target genes depends on the Drosophila homolog of the CBP histone acetyltransferase.

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Capturing large genomic contexts for accurately predicting enhancer-promoter interactions

10.1101/2021.09.04.458817 ◽

2021 ◽

Author(s):

Ken Chen ◽

Huiying Zhao ◽

Yuedong Yang

Keyword(s):

Target Gene ◽

Target Genes ◽

Cell Types ◽

Training Data ◽

Independent Test ◽

Distant Target ◽

Comparable Performance ◽

Precision Recall Curve ◽

Different Cell Types ◽

The Impact

AbstractAccurately identifying enhancer-promoter interactions (EPIs) is challenging because enhancers usually act on the promoters of distant target genes. Although a variety of machine learning and deep learning models have been developed, many of them are not designed to or could not be well applied to predict EPIs in cell types different from the training data. In this study, we develop the TransEPI model for EPI prediction based on datasets derived from Hi-C and ChIA-PET data. TransEPI compiles genomic features from large intervals harboring the enhancer-promoter pair and adopts a Transformer-based architecture to capture the long-range dependencies. Thus, TransEPI could achieve more accurate prediction by addressing the impact of other genomic loci that may competitively interact with the enhancer-promoter pair. We evaluate TransEPI in a challenging scenario, where the independent test samples are predicted by models trained on the data from different cell types and chromosomes. TransEPI robustly predicts cross-cell-type EPI prediction by achieving comparable performance in cross-validation and independent test. More importantly, TransEPI significantly outperforms the state-of-the-art EPI models on the independent test datasets, with the Area Under Precision-Recall Curve (auPRC) score increasing by 48.84 % on average. Hence, TransEPI is applicable for accurate EPI prediction in cell types without chromatin structure data. Moreover, we find the TransEPI framework could also be extended to identify the target gene of non-coding mutations, which may facilitate studying pathogenic non-coding mutations.

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Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

10.20944/preprints202004.0241.v1 ◽

2020 ◽

Author(s):

Shicheng Guo ◽

Cen Chang ◽

Lingxia Xu ◽

Runrun Zhang ◽

Yehua Jin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Therapeutic Intervention ◽

Target Genes ◽

Cell Types ◽

Micro Rna ◽

Current Evidence ◽

Diagnosis And Prognosis ◽

Transcriptome Regulation ◽

Therapy Target ◽

Different Cell Types

micro-RNA (miRNA) has been demonstrated to play important roles in the transcriptome regulation and disease development including cancer and autoimmune disease such as rheumatoid arthritis. However, a comprehensive map on how the mRNAs regulate transcripts, pathways, immune system differentiation and interaction with terminal cells like T-cells, fibroblast-like synoviocytes (FLS), osteoblast and osteoclast still unknown. In this review, we have provided a thorough summary on the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention and prognosis. Numerous miRNAs were found abnormally expressed in rheumatoid arthritis relevant cells and regulated the target genes and pathways like NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, mTOR pathway. In addition, miRNA act as gene expression regulators affect the T-cell differentiate to different cell types including Th17 and T-reg cells which provide promising gene therapy target to regulate immune systems in rheumatoid arthritis. We also summarized interesting diagnosis and prognosis roles of blood and cell-free based miRNAs which provided novel opportunity to work together with rheumatoid factors (RF), anti-CCP to provide accurate diagnosis and prognosis especially for seronegative patients. Furthermore, functional genetic variants in miRNA-499 and miRNA-146a explained part of missing susceptibility of rheumatoid arthritis. Finally, miRNAs were showed as promising biomarker to indicate the DMRDS and immunotherapy efficiency, drug response and resistance. What’s more, autotherapeutic effect of miRNA intervention provided promising to develop miRNA based rheumatoid arthritis drugs. Overall, current evidence supports miRNAs as the interesting targets to better understand the pathogenetic mechanism and therapeutic intervention of rheumatoid arthritis.

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Specific Regulatory Motifs Predict Glucocorticoid Responsiveness of Hippocampal Gene Expression

Endocrinology ◽

10.1210/en.2011-0287 ◽

2011 ◽

Vol 152 (10) ◽

pp. 3749-3757 ◽

Cited By ~ 46

Author(s):

N. A. Datson ◽

J. A. E. Polman ◽

R. T. de Jonge ◽

P. T. M. van Boheemen ◽

E. M. T. van Maanen ◽

...

Keyword(s):

Target Genes ◽

Zinc Finger Protein ◽

Cell Types ◽

Nucleotide Composition ◽

Rat Hippocampus ◽

Glucocorticoid Response ◽

Direct Binding ◽

Flanking Sequences ◽

Different Cell Types ◽

High Degree

The glucocorticoid receptor (GR) is an ubiquitously expressed ligand-activated transcription factor that mediates effects of cortisol in relation to adaptation to stress. In the brain, GR affects the hippocampus to modulate memory processes through direct binding to glucocorticoid response elements (GREs) in the DNA. However, its effects are to a high degree cell specific, and its target genes in different cell types as well as the mechanisms conferring this specificity are largely unknown. To gain insight in hippocampal GR signaling, we characterized to which GRE GR binds in the rat hippocampus. Using a position-specific scoring matrix, we identified evolutionary-conserved putative GREs from a microarray based set of hippocampal target genes. Using chromatin immunoprecipitation, we were able to confirm GR binding to 15 out of a selection of 32 predicted sites (47%). The majority of these 15 GREs are previously undescribed and thus represent novel GREs that bind GR and therefore may be functional in the rat hippocampus. GRE nucleotide composition was not predictive for binding of GR to a GRE. A search for conserved flanking sequences that may predict GR-GRE interaction resulted in the identification of GC-box associated motifs, such as Myc-associated zinc finger protein 1, within 2 kb of GREs with GR binding in the hippocampus. This enrichment was not present around nonbinding GRE sequences nor around proven GR-binding sites from a mesenchymal stem-like cell dataset that we analyzed. GC-binding transcription factors therefore may be unique partners for DNA-bound GR and may in part explain cell-specific transcriptional regulation by glucocorticoids in the context of the hippocampus.

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The Role of MicroRNAs in Regulatory T Cells

Journal of Immunology Research ◽

10.1155/2020/3232061 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Chao Liu ◽

Nannan Li ◽

Guijian Liu

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Small Rnas ◽

Target Genes ◽

Cell Types ◽

Immune Disorders ◽

Ongoing Research ◽

Different Cell Types

MicroRNAs are a class of conserved, 20 nt-23 nt long, noncoding small RNAs that inhibit expression of their respective target genes in different cell types. Regulatory T cells (Tregs) are a subpopulation of T cells that negatively regulate immune responses, which is essential to immune homeostasis. Recent studies have indicated that microRNAs play an important role in the proliferation, differentiation, and functions of Treg. Here, we review the recent progress in understanding the roles of microRNAs in Treg and their dysregulation in immune-related diseases. This ongoing research continues to expand the understanding of Treg regulation and the mechanisms of immune disorders.

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Unveiling the ups and downs of miR-205 in physiology and cancer: transcriptional and post-transcriptional mechanisms

Cell Death and Disease ◽

10.1038/s41419-020-03192-4 ◽

2020 ◽

Vol 11 (11) ◽

Author(s):

Elena Ferrari ◽

Paolo Gandellini

Keyword(s):

Epithelial Cell ◽

Target Genes ◽

Cell Function ◽

Cell Types ◽

Future Application ◽

Transcriptional Level ◽

Aberrant Expression ◽

Specific Tumor ◽

And Function ◽

Different Cell Types

Abstract miR-205 plays important roles in the physiology of epithelia by regulating a variety of pathways that govern differentiation and morphogenesis. Its aberrant expression is frequently found in human cancers, where it was reported to act either as tumor-suppressor or oncogene depending on the specific tumor context and target genes. miR-205 expression and function in different cell types or processes are the result of the complex balance among transcription, processing and stability of the microRNA. In this review, we summarize the principal mechanisms that regulate miR-205 expression at the transcriptional and post-transcriptional level, with particular focus on the transcriptional relationship with its host gene. Elucidating the mechanisms and factors regulating miR-205 expression in different biological contexts represents a fundamental step for a better understanding of the contribution of such pivotal microRNA to epithelial cell function in physiology and disease, and for the development of modulation strategies for future application in cancer therapy.

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Prediction of Drug Efficacy in Colon Cancer Preclinical Models Using a Novel Ranking Method of Gene Expression

Cancers ◽

10.3390/cancers12010149 ◽

2020 ◽

Vol 12 (1) ◽

pp. 149

Author(s):

Justine Fritz ◽

Olivier Lefebvre ◽

Aurore Fernandez ◽

Jordane Schmidt ◽

Dominique Bagnard

Keyword(s):

Gene Expression ◽

Target Gene ◽

Target Genes ◽

Drug Efficacy ◽

Standard Of Care ◽

Cell Types ◽

Efficient Treatment ◽

Tumor Types ◽

Different Cell Types ◽

Reference Samples

The presence of stromal cells in tumors is altering the significance of molecular profiling when using standard methods of gene expression quantification. We developed a novel normalization method to rank target gene expression in tumor samples by comparisons with reference samples representing the different cell types found in a tumor. The score for each target gene obtained after normalization, is aimed to be predictive of targeted therapies efficiency. We performed this qPCR analysis on human colorectal cancers to demonstrate the importance of reference samples to obtain accurate data and on a collection of patient-derived xenografted (PDX) colon tumors treated with Cetuximab (anti-EGFR) to demonstrate that the calculated EGFR score is predictive of Cetuximab efficacy. Interestingly, the score allowed to select an efficient treatment in a PDX model refractory to standard of care. This method is opening a novel way to predict targeted therapy efficiency which could be extended to several tumor types, and to unlimited target genes.

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Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053310 ◽

1982 ◽

Vol 40 ◽

pp. 118-119

Author(s):

U. Aebi ◽

P. Rew ◽

T.-T. Sun

Keyword(s):

Electron Microscopy ◽

Structural Organization ◽

Cell Types ◽

Structural Features ◽

Molecular Architecture ◽

The Past ◽

Keratin Filaments ◽

Different Types ◽

10 Nm Filaments ◽

Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

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Processing and Characterization of Recombinant von Willebrand Factor Expressed in Different Cell Types Using a Vaccinia Virus Vector

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648398 ◽

1992 ◽

Vol 67 (01) ◽

pp. 154-160 ◽

Cited By ~ 14

Author(s):

P Meulien ◽

M Nishino ◽

C Mazurier ◽

K Dott ◽

G Piétu ◽

...

Keyword(s):

Vaccinia Virus ◽

Von Willebrand Factor ◽

Human Fibroblasts ◽

Active Form ◽

Cell Types ◽

Biologically Active ◽

L Cells ◽

Von Willebrand ◽

Different Cell Types ◽

Willebrand Factor

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.

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Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽

10.32607/20758251-2016-8-2-79-86 ◽

2016 ◽

Vol 8 (2) ◽

pp. 79-86 ◽

Cited By ~ 3

Author(s):

P. V. Elizar’ev ◽

D. V. Lomaev ◽

D. A. Chetverina ◽

P. G. Georgiev ◽

M. M. Erokhin

Keyword(s):

Dna Sequences ◽

Cell Types ◽

Transcription Terminator ◽

Response Elements ◽

Polycomb Response Elements ◽

The Individual ◽

Multicellular Organisms ◽

Different Cell Types ◽

Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

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