scholarly journals Computational modeling of chromatin accessibility identified important epigenomic regulators

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yanding Zhao ◽  
Yadong Dong ◽  
Wei Hong ◽  
Chongming Jiang ◽  
Kevin Yao ◽  
...  
Keyword(s):  
Cell Line ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Chromatin Accessibility ◽  
High Accuracy ◽  
Combined Model ◽  
Transcription Start Sites ◽  
A Cell ◽  
Limited Power ◽  
Genomic Regions

AbstractChromatin accessibility is essential for transcriptional activation of genomic regions. It is well established that transcription factors (TFs) and histone modifications (HMs) play critical roles in chromatin accessibility regulation. However, there is a lack of studies that quantify these relationships. Here we constructed a two-layer model to predict chromatin accessibility by integrating DNA sequence, TF binding, and HM signals. By applying the model to two human cell lines (GM12878 and HepG2), we found that DNA sequences had limited power for accessibility prediction, while both TF binding and HM signals predicted chromatin accessibility with high accuracy. According to the HM model, HM features determined chromatin accessibility in a cell line shared manner, with the prediction power attributing to five core HM types. Results from the TF model indicated that chromatin accessibility was determined by a subset of informative TFs including both cell line-specific and generic TFs. The combined model of both TF and HM signals did not further improve the prediction accuracy, indicating that they provide redundant information in terms of chromatin accessibility prediction. The TFs and HM models can also distinguish the chromatin accessibility of proximal versus distal transcription start sites with high accuracy.

scholarly journals Computational Modeling of Chromatin Accessibility Identified Important Epigenomic Regulators

2021 ◽  
Author(s):  
Yanding Zhao ◽  
Yadong Dong ◽  
Wei Hong ◽  
Chongming Jiang ◽  
Kevin Yao ◽  
...  
Keyword(s):  
Cell Line ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Chromatin Accessibility ◽  
High Accuracy ◽  
Combined Model ◽  
Transcription Start Sites ◽  
A Cell ◽  
Limited Power ◽  
Genomic Regions

Abstract Chromatin accessibility is essential for transcriptional activation of genomic regions. It is well established that transcription factors (TFs) and histone modifications (HMs) play critical roles in chromatin accessibility regulation. However, there is a lack of studies that quantify these relationships. Here we constructed a two-layer model to predict chromatin accessibility by integrating DNA sequence, TF binding, and HM signals. By applying the model to two human cell lines (GM12878 and HepG2), we found that DNA sequences had limited power for accessibility prediction, while both TF binding and HM signals predicted chromatin accessibility with high accuracy. According to the HM model, HM features determined chromatin accessibility in a cell line shared manner, with the prediction power attributing to five core HM types. Results from the TF model indicated that chromatin accessibility was determined by a subset of informative TFs including both cell line-specific and generic TFs. The combined model of both TF and HM signals did not further improve the prediction accuracy, indicating that they provide redundant information in terms of chromatin accessibility prediction. The TFs and HM models can also distinguish the chromatin accessibility of proximal versus distal transcription start sites with high accuracy.

scholarly journals The Poly(C) Motif in the Proximal Promoter Region of the D Site-Binding Protein Gene (Dbp) Drives Its High-Amplitude Oscillation

2019 ◽  
Vol 39 (16) ◽  
Author(s):  
Paul Kwangho Kwon ◽  
Hyo-Min Kim ◽  
Sung Wook Kim ◽  
Byunghee Kang ◽  
Hee Yi ◽  
...  
Keyword(s):  
Cell Line ◽  
Transcriptional Activation ◽  
Clock Genes ◽  
Binding Protein ◽  
Oscillation Amplitude ◽  
Underlying Mechanism ◽  
High Amplitude ◽  
Chromatin Accessibility ◽  
Proximal Promoter ◽  
Site Binding

ABSTRACT The D site-binding protein (Dbp) supports the rhythmic transcription of downstream genes, in part by displaying high-amplitude cycling of its own transcripts compared to other circadian-clock genes. However, the underlying mechanism remains elusive. Here, we demonstrated that the poly(C) motif within the Dbp proximal promoter, in addition to an E-box element, provoked transcriptional activation. Furthermore, we generated a cell line with poly(C) deleted to demonstrate the endogenous effect of the poly(C) motif within the Dbp promoter. We investigated whether RNA polymerase 2 (Pol2) recruitment on the Dbp promoter was decreased in the cell line with poly(C) deleted. Next, assay for transposase-accessible chromatin (ATAC)-quantitative PCR (qPCR) showed that the poly(C) motif induced greater chromatin accessibility within the region of the Dbp promoter. Finally, we determined that the oscillation amplitude of endogenous Dbp mRNA of the cell line with poly(C) deleted was decreased, which affected the oscillation of other clock genes that are controlled by Dbp. Taken together, our results provide new insights into the function of the poly(C) motif as a novel cis-acting element of Dbp, along with its significance in the regulation of circadian rhythms.

scholarly journals Human SWI/SNF-Associated PRMT5 Methylates Histone H3 Arginine 8 and Negatively Regulates Expression of ST7 and NM23 Tumor Suppressor Genes

2004 ◽  
Vol 24 (21) ◽  
pp. 9630-9645 ◽  
Author(s):  
Sharmistha Pal ◽  
Sheethal N. Vishwanath ◽  
Hediye Erdjument-Bromage ◽  
Paul Tempst ◽  
Saïd Sif
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Transcriptional Activation ◽  
Tumor Suppressor Genes ◽  
Chromatin Remodelers ◽  
Protein Arginine Methyltransferases ◽  
Expression Of Genes ◽  
A Cell ◽  
Cell Growth And Proliferation ◽  
Nih 3T3

ABSTRACT Protein arginine methyltransferases (PRMTs) have been implicated in transcriptional activation and repression, but their role in controlling cell growth and proliferation remains obscure. We have recently shown that PRMT5 can interact with flag-tagged BRG1- and hBRM-based hSWI/SNF chromatin remodelers and that both complexes can specifically methylate histones H3 and H4. Here we report that PRMT5 can be found in association with endogenous hSWI/SNF complexes, which can methylate H3 and H4 N-terminal tails, and show that H3 arginine 8 and H4 arginine 3 are preferred sites of methylation by recombinant and hSWI/SNF-associated PRMT5. To elucidate the role played by PRMT5 in gene regulation, we have established a PRMT5 antisense cell line and determined by microarray analysis that more genes are derepressed when PRMT5 levels are reduced. Among the affected genes, we show that suppressor of tumorigenicity 7 (ST7) and nonmetastatic 23 (NM23) are direct targets of PRMT5-containing BRG1 and hBRM complexes. Furthermore, we demonstrate that expression of ST7 and NM23 is reduced in a cell line that overexpresses PRMT5 and that this decrease in expression correlates with H3R8 methylation, H3K9 deacetylation, and increased transformation of NIH 3T3 cells. These findings suggest that the BRG1- and hBRM-associated PRMT5 regulates cell growth and proliferation by controlling expression of genes involved in tumor suppression.

scholarly journals Identification and prediction of developmental enhancers in sea urchin embryos

2021 ◽  
Author(s):  
Cesar Arenas-Mena ◽  
Sofija Miljovska ◽  
Sevinc Ercan ◽  
Tanvi Shashikant ◽  
Charles G. Danko ◽  
...  
Keyword(s):  
Sea Urchin ◽  
Transcriptional Activation ◽  
Functional Characterization ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Model Organisms ◽  
Enhancer Activity ◽  
Pol Ii ◽  
Sea Urchin Embryos ◽  
Genomic Regions

The transcription of developmental regulatory genes is often controlled by multiple cis-regulatory elements. The identification and functional characterization of distal regulatory elements remains challenging, even in tractable model organisms like sea urchins. We evaluate the use of chromatin accessibility, transcription and RNA Polymerase II for their ability to predict enhancer activity of genomic regions in sea urchin embryos. ATAC-seq, PRO-seq, and Pol II ChIP-seq from early and late blastula embryos are manually contrasted with experimental cis-regulatory analyses available in sea urchin embryos, with particular attention to common developmental regulatory elements known to have enhancer and silencer functions differentially deployed among embryonic territories. Using the three functional genomic data types, machine learning models are trained and tested to classify and quantitatively predict the enhancer activity of several hundred genomic regions previously validated with reporter constructs in vivo. Overall, chromatin accessibility and transcription have substantial power for predicting enhancer activity. For promoter-overlapping cis-regulatory elements in particular, the distribution of Pol II is the best predictor of enhancer activity in blastula embryos. Furthermore, ATAC- and PRO-seq predictive value is stage dependent for the promoter-overlapping subset. This suggests that the sequence of regulatory mechanisms leading to transcriptional activation have distinct relevance at different levels of the developmental gene regulatory hierarchy deployed during embryogenesis.

scholarly journals Chromosomal Insertion and Amplification of Human Papillomavirus 16 DNA Sequences in a Cell Line of Argyrophil Small Cell Carcinoma of the Uterine Cervix

1991 ◽  
Vol 82 (4) ◽  
pp. 371-375 ◽  
Author(s):  
Tada-aki Hori ◽  
Hiroshi Ichimura ◽  
Masako Minamihisamatsu ◽  
Ei-ichi Takahashi ◽  
Masatake Yamauchi ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Small Cell Carcinoma ◽  
Dna Sequences ◽  
Uterine Cervix ◽  
Small Cell ◽  
Human Papillomavirus 16 ◽  
A Cell

scholarly journals Measuring DNA mechanics on the genome scale

2020 ◽  
Author(s):  
Aakash Basu ◽  
Dmitriy G. Bobrovnikov ◽  
Zan Qureshi ◽  
Tunc Kayikcioglu ◽  
Thuy T. M. Ngo ◽  
...  
Keyword(s):  
High Throughput ◽  
Dna Sequences ◽  
Cellular Functions ◽  
Dna Mechanics ◽  
Transcription Start Sites ◽  
Mechanical Deformations ◽  
Nucleosome Formation ◽  
Genomic Regions ◽  
Genome Scale ◽  
Dna Bendability

AbstractMechanical deformations of DNA such as bending are ubiquitous and implicated in diverse cellular functions1. However, the lack of high-throughput tools to directly measure the mechanical properties of DNA limits our understanding of whether and how DNA sequences modulate DNA mechanics and associated chromatin transactions genome-wide. We developed an assay called loop-seq to measure the intrinsic cyclizability of DNA – a proxy for DNA bendability – in high throughput. We measured the intrinsic cyclizabilities of 270,806 50 bp DNA fragments that span the entire length of S. cerevisiae chromosome V and other genomic regions, and also include random sequences. We discovered sequence-encoded regions of unusually low bendability upstream of Transcription Start Sites (TSSs). These regions disfavor the sharp DNA bending required for nucleosome formation and are co-centric with known Nucleosome Depleted Regions (NDRs). We show biochemically that low bendability of linker DNA located about 40 bp away from a nucleosome edge inhibits nucleosome sliding into the linker by the chromatin remodeler INO80. The observation explains how INO80 can create promoter-proximal nucleosomal arrays in the absence of any other factors2 by reading the DNA mechanical landscape. We show that chromosome wide, nucleosomes are characterized by high DNA bendability near dyads and low bendability near the linkers. This contrast increases for nucleosomes deeper into gene bodies, suggesting that DNA mechanics plays a previously unappreciated role in organizing nucleosomes far from the TSS, where nucleosome remodelers predominate. Importantly, random substitution of synonymous codons does not preserve this contrast, suggesting that the evolution of codon choice has been impacted by selective pressure to preserve sequence-encoded mechanical modulations along genes. We also provide evidence that transcription through the TSS-proximal nucleosomes is impacted by local DNA mechanics. Overall, this first genome-scale map of DNA mechanics hints at a ‘mechanical code’ with broad functional implications.

scholarly journals DeepCAPE: a deep convolutional neural network for the accurate prediction of enhancers

2018 ◽  
Author(s):  
Shengquan Chen ◽  
Mingxin Gan ◽  
Hairong Lv ◽  
Rui Jiang
Keyword(s):  
Neural Network ◽  
Convolutional Neural Network ◽  
Cell Line ◽  
Cell Lines ◽  
Dna Sequences ◽  
Disease Status ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Deep Convolutional Neural Network ◽  
Typical Cell

AbstractThe establishment of a landscape of enhancers across human cells is crucial to deciphering the mechanism of gene regulation, cell differentiation, and disease development. High-throughput experimental approaches, though having successfully reported enhancers in typical cell lines, are still too costly and time consuming to perform systematic identification of enhancers specific to different cell lines under a variety of disease status. Existing computational methods, though capable of predicting regulatory elements purely relying on DNA sequences, lack the power of cell line-specific screening. Recent studies have suggested that chromatin accessibility of a DNA segment is closely related to its potential function in regulation, and thus may provide useful information in identifying regulatory elements. Motivated by the above understanding, we integrate DNA sequences and chromatin accessibility data to accurately predict enhancers in a cell line-specific manner. We proposed DeepCAPE, a deep convolutional neural network to predict enhancers via the integration of DNA sequences and DNase-seq data. We demonstrate that our model not only consistently outperforms existing methods in the classification of enhancers against background sequences, but also accurately predicts enhancers across different cell lines. We further visualize kernels of the first convolutional layer and show the match of identified sequence signatures and known motifs. We finally demonstrate the potential ability of our model to explain functional implications of putative disease-associated genetic variants and discriminate disease-related enhancers.

Aberrant Type C Virus Production in a Cell Line Derived from Balb/3T3

1972 ◽  
Vol 30 ◽  
pp. 286-287
Author(s):  
N. Savage ◽  
A. Hackett
Keyword(s):  
Electron Microscopy ◽  
Cell Line ◽  
Leukemia Virus ◽  
Morphological Characteristics ◽  
Virus Production ◽  
Oncogenic Viruses ◽  
Endogenous Virus ◽  
Virus Particles ◽  
Moloney Leukemia Virus ◽  
A Cell

A cell line, UC1-B, which was derived from Balb/3T3 cells, maintains the same morphological characteristics of the non-transformed parental culture, and shows no evidence of spontaneous virus production. Survey by electron microscopy shows that the cell line consists of spindle-shaped cells with no unusual features and no endogenous virus particles.UC1-B cells respond to Moloney leukemia virus (MLV) infection by a change in morphology and growth pattern which is typical of cells transformed by sarcoma virus. Electron microscopy shows that the cells are now variable in shape (rounded, rhomboid, and spindle), and each cell type has some microvilli. Virtually all (90%) of the cells show virus particles developing at the cell surface and within the cytoplasm. Maturing viruses, typical of the oncogenic viruses, are found along with atypical tubular forms in the same cell.

Establishment of a cell line (HCC-M) from a human hepatocellular carcinoma

1983 ◽  
Vol 32 (2) ◽  
pp. 141-146 ◽  
Author(s):  
Tetsu Watanabe ◽  
Toshio Morizane ◽  
Kanji Tsuchimoto ◽  
Yasutaka Inagaki ◽  
Yoshio Munakata ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Human Hepatocellular Carcinoma ◽  
A Cell

scholarly journals A Yeast taf17 Mutant Requires the Swi6 Transcriptional Activator for Viability and Shows Defects in Cell Cycle-Regulated Transcription

Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1561-1576
Author(s):  
Neil Macpherson ◽  
Vivien Measday ◽  
Lynda Moore ◽  
Brenda Andrews
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Essential Gene ◽  
Temperature Sensitive ◽  
Permissive Temperature ◽  
Synthetic Lethal ◽  
Cycle Arrest ◽  
A Cell ◽  
Allelism Tests ◽  
Complementation Groups

Abstract In Saccharomyces cerevisiae, the Swi6 protein is a component of two transcription factors, SBF and MBF, that promote expression of a large group of genes in the late G1 phase of the cell cycle. Although SBF is required for cell viability, SWI6 is not an essential gene. We performed a synthetic lethal screen to identify genes required for viability in the absence of SWI6 and identified 10 complementation groups of swi6-dependent lethal mutants, designated SLM1 through SLM10. We were most interested in mutants showing a cell cycle arrest phenotype; both slm7-1 swi6Δ and slm8-1 swi6Δ double mutants accumulated as large, unbudded cells with increased 1N DNA content and showed a temperature-sensitive growth arrest in the presence of Swi6. Analysis of the transcript levels of cell cycle-regulated genes in slm7-1 SWI6 mutant strains at the permissive temperature revealed defects in regulation of a subset of cyclin-encoding genes. Complementation and allelism tests showed that SLM7 is allelic with the TAF17 gene, which encodes a histone-like component of the general transcription factor TFIID and the SAGA histone acetyltransferase complex. Sequencing showed that the slm7-1 allele of TAF17 is predicted to encode a version of Taf17 that is truncated within a highly conserved region. The cell cycle and transcriptional defects caused by taf17slm7-1 are consistent with the role of TAFIIs as modulators of transcriptional activation and may reflect a role for TAF17 in regulating activation by SBF and MBF.

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