scholarly journals The borders of cis-regulatory DNA sequences harbor the divergent transcription factor binding motifs in the human genome

2018 ◽  
Author(s):  
Jia-Hsin Huang ◽  
Ryan Shun-Yuen Kwan ◽  
Zing Tsung-Yeh Tsai ◽  
Huai-Kuang Tsai
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Dynamic Change ◽  
Evolutionary Divergence ◽  
Evolutionary Time ◽  
Regulatory Regions ◽  
Binding Motifs ◽  
Regulatory Dna Sequences ◽  
Hypersensitive Sites ◽  
Regulatory Dna

AbstractChanges in the cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources that shape the gene regulatory evolution in eukaryotes. However, it is currently unclear how dynamic change of DNA sequences introduce various divergence level of TF binding motifs in the genome over evolutionary time. Here, we estimated the evolutionary divergence level of the TF binding motifs, and quantified their occurrences in the DNase I hypersensitive sites. Results from our in silico motif scan and empirical TF-ChIP (chromatin immunoprecipitation) demonstrate that the divergent motifs tend to be introduced at the borders of the cis-regulatory regions, that are likely accompanied with the expansion through evolutionary time. Accordingly, we propose that an expansion by incorporating divergent motifs within the cis-regulatory regions provides a rationale for the evolutionary divergence of regulatory circuits.

scholarly journals Role of Transcription Factor Kar4 in Regulating Downstream Events in the Saccharomyces cerevisiae Pheromone Response Pathway

2006 ◽  
Vol 27 (3) ◽  
pp. 818-829 ◽  
Author(s):  
Ron Lahav ◽  
Alison Gammie ◽  
Saeed Tavazoie ◽  
Mark D. Rose
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Critical Role ◽  
Gene Clusters ◽  
Sequence Motif ◽  
Dependent Manner ◽  
Regulatory Dna Sequences ◽  
Putative Transcription Factor ◽  
Regulatory Dna

ABSTRACT Yeast Kar4 is a putative transcription factor required for karyogamy (the fusion of haploid nuclei during mating) and possibly other functions. Previously known to be required only for the transcriptional induction of KAR3 and CIK1, microarray experiments identified many genes regulated by Kar4 in both mating and mitosis. Several gene clusters are positively or negatively regulated by mating pheromone in a Kar4-dependent manner. Chromatin immunoprecipitation and gel shift assays confirmed that Kar4 binds to regulatory DNA sequences upstream of KAR3. Together with one-hybrid experiments, these data support a model in which both Kar4 and Ste12 bind jointly to the KAR3 promoter. Analysis of the upstream regions of Kar4-induced genes identified a DNA sequence motif that may be a binding site for Kar4. Mutation within the motif upstream of KAR3 eliminated pheromone induction. Genes regulated by Kar4, on average, are delayed in their temporal expression and exhibit a more stringent dose response to pheromone. Furthermore, the induction of Kar4 by pheromone is necessary for the delayed temporal induction of KAR3 and PRM2, genes required for efficient nuclear fusion during mating. Accordingly, we propose that Kar4 plays a critical role in the choreography of the mating response.

scholarly journals Deciphering regulatory DNA sequences and noncoding genetic variants using neural network models of massively parallel reporter assays

PLoS ONE ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. e0218073 ◽  
Author(s):  
Rajiv Movva ◽  
Peyton Greenside ◽  
Georgi K. Marinov ◽  
Surag Nair ◽  
Avanti Shrikumar ◽  
...  
Keyword(s):  
Neural Network ◽  
Dna Sequences ◽  
Genetic Variants ◽  
Network Models ◽  
Massively Parallel ◽  
Neural Network Models ◽  
Regulatory Dna Sequences ◽  
Reporter Assays ◽  
Regulatory Dna

Functional Comparison of the Upstream Regulatory DNA Sequences of Four Human Epidermal Keratin Genes

1991 ◽  
Vol 96 (2) ◽  
pp. 162-167 ◽  
Author(s):  
Chuan-Kui Jiang ◽  
Howard S Epstein ◽  
Marjana Tomic ◽  
Irwin M Freedberg ◽  
Miroslav Blumenberg
Keyword(s):  
Dna Sequences ◽  
Regulatory Dna Sequences ◽  
Regulatory Dna

scholarly journals Deciphering regulatory DNA sequences and noncoding genetic variants using neural network models of massively parallel reporter assays

2018 ◽  
Author(s):  
Rajiv Movva ◽  
Peyton Greenside ◽  
Georgi K. Marinov ◽  
Surag Nair ◽  
Avanti Shrikumar ◽  
...  
Keyword(s):  
Neural Network ◽  
Dna Sequences ◽  
Genetic Variants ◽  
Massively Parallel ◽  
Regulatory Sequence ◽  
Regulatory Activity ◽  
Neural Network Models ◽  
Regulatory Dna Sequences ◽  
Reporter Assays ◽  
Regulatory Dna

AbstractThe relationship between noncoding DNA sequence and gene expression is not well-understood. Massively parallel reporter assays (MPRAs), which quantify the regulatory activity of large libraries of DNA sequences in parallel, are a powerful approach to characterize this relationship. We present MPRA-DragoNN, a convolutional neural network (CNN)-based framework to predict and interpret the regulatory activity of DNA sequences as measured by MPRAs. While our method is generally applicable to a variety of MPRA designs, here we trained our model on the Sharpr-MPRA dataset that measures the activity of ~500,000 constructs tiling 15,720 regulatory regions in human K562 and HepG2 cell lines. MPRA-DragoNN predictions were moderately correlated (Spearman ρ = 0.28) with measured activity and were within range of replicate concordance of the assay. State-of-the-art model interpretation methods revealed high-resolution predictive regulatory sequence features that overlapped transcription factor (TF) binding motifs. We used the model to investigate the cell type and chromatin state preferences of predictive TF motifs. We explored the ability of our model to predict the allelic effects of regulatory variants in an independent MPRA experiment and fine map putative functional SNPs in loci associated with lipid traits. Our results suggest that interpretable deep learning models trained on MPRA data have the potential to reveal meaningful patterns in regulatory DNA sequences and prioritize regulatory genetic variants, especially as larger, higher-quality datasets are produced.

scholarly journals The role of maternal pioneer factors in predefining first zygotic responses to inductive signals

2018 ◽  
Author(s):  
George E. Gentsch ◽  
Thomas Spruce ◽  
Nick D. L. Owens ◽  
James C. Smith
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Regulatory Elements ◽  
Regulatory Dna Sequences ◽  
Cell Type Specific ◽  
Pioneer Factors ◽  
Developmental Principles ◽  
Regulatory Dna ◽  
Different Cell Types ◽  
Inductive Signals

ABSTRACTEmbryonic development yields many different cell types in response to just a few families of inductive signals. The property of a signal-receiving cell that determines how it responds to such signals, including the activation of cell type-specific genes, is known as its competence. Here, we show how maternal factors modify chromatin to specify initial competence in the frog Xenopus tropicalis. We identified the earliest engaged regulatory DNA sequences, and inferred from them critical activators of the zygotic genome. Of these, we showed that the pioneering activity of the maternal pluripotency factors Pou5f3 and Sox3 predefines competence for germ layer formation by extensively remodeling compacted chromatin before the onset of signaling. The remodeling includes the opening and marking of thousands of regulatory elements, extensive chromatin looping, and the co-recruitment of signal-mediating transcription factors. Our work identifies significant developmental principles that inform our understanding of how pluripotent stem cells interpret inductive signals.

Nuclear receptors and disease: androgen receptor

2004 ◽  
Vol 40 ◽  
pp. 121-136 ◽  
Author(s):  
Bruce Gottlieb ◽  
Lenore K Beitel ◽  
Jianhui Wu ◽  
Youssef A Elhaji ◽  
Mark Trifiro
Keyword(s):  
Androgen Receptor ◽  
Dna Sequences ◽  
Muscular Atrophy ◽  
Binding Domain ◽  
Spinobulbar Muscular Atrophy ◽  
Precise Control ◽  
Research Areas ◽  
Regulatory Dna Sequences ◽  
Active Research ◽  
Regulatory Dna

The androgen receptor (AR) protein regulates transcription of certain genes. Usually this depends upon a central DNA-binding domain that permits the binding of androgen–AR complexes to regulatory DNA sequences near or in a target gene. The AR also has a C-terminal ligand-binding domain and an Nterminal transcription modulatory domain. These N- and C-terminal domains interact directly, and with co-regulatory, non-receptor proteins, to exert precise control over a gene’s transcription rate. The precise roles of these proteins are active research areas. Severe X-linked AR gene (AR) mutations cause complete androgen insensitivity, mild ones impair virilization with or without infertility, and moderate ones yield a wide phenotypic spectrum sometimes among siblings. Different phenotype expressivity may reflect variability of ARinteractive proteins. Mutations occur throughout the AR but are concentrated in specific areas of the gene known as hot spots. A number of these mutations of somatic origin are associated with prostate cancer. N-terminal polyglutamine (polyGln) tract expansion reduces AR transactivation, and when there are more than 38 glutamine residues it causes spinobulbar muscular atrophy, a motor neuron disease, due to a gain of function. Variations in polyGln tract length have been associated as risk factors with prostate, breast, uterine, endometrial and colorectal cancer, as well as male infertility.

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