Transcription factor ZmNAC126 plays an important role in transcriptional regulation of maize starch synthesis-related genes

AbstractWhile transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis of transcription factor binding and transcriptomic data to identify transposon-derived promoters that are activated in specific diseases and developmental states. We applied this pipeline to a breast cancer model, and found that the L1PA2 transposon subfamily contributes abundant regulatory sequences to co-ordinated transcriptional regulation in breast cancer. Transcription factor profiling demonstrates that over 27% of L1PA2 transposons harbour co-localised binding sites of functionally interacting, cancer-associated transcription factors in MCF7 cells, a cell line used to model breast cancer. Transcriptomic analysis reveals that L1PA2 transposons also contribute transcription start sites to up-regulated transcripts in MCF7 cells, including some transcripts with established oncogenic properties. In addition, we verified the utility of our pipeline on other transposon subfamilies, as well as on leukemia and lung carcinoma cell lines. We demonstrate that the normally quiescent regulatory activities of transposons can be activated and alter the cancer transcriptome. In particular, the L1PA2 subfamily contributes abundant regulatory sequences, and likely plays a global role in modulating breast cancer transcriptional regulation. Understanding the regulatory impact of L1PA2 on breast cancer genomes provides additional insights into cancer genome regulation, and may provide novel biomarkers for disease diagnosis, prognosis and therapy.

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Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources

BMC Bioinformatics ◽

10.1186/s12859-021-04126-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Neel Patel ◽

William S. Bush

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Regulation ◽

Gene Regulatory Networks ◽

Regulatory Networks ◽

Prediction Models ◽

Long Distance ◽

Chromatin Looping ◽

Gene Regulatory ◽

The Impact

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

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A Genetic Screen of the Drosophila X Chromosome for Mutations That Modify Deformed Function

Genetics ◽

10.1093/genetics/150.4.1497 ◽

1998 ◽

Vol 150 (4) ◽

pp. 1497-1511 ◽

Cited By ~ 1

Author(s):

Brian Florence ◽

William McGinnis

Keyword(s):

Transcription Factor ◽

Transcriptional Regulation ◽

Cell Signaling ◽

X Chromosome ◽

Adaptor Protein ◽

Genetic Screen ◽

The Other ◽

Homeotic Gene ◽

Hox Proteins ◽

Hox Gene

Abstract We have screened the Drosophila X chromosome for genes whose dosage affects the function of the homeotic gene Deformed. One of these genes, extradenticle, encodes a homeodomain transcription factor that heterodimerizes with Deformed and other homeotic Hox proteins. Mutations in the nejire gene, which encodes a transcriptional adaptor protein belonging to the CBP/p300 family, also interact with Deformed. The other previously characterized gene identified as a Deformed interactor is Notch, which encodes a transmembrane receptor. These three genes underscore the importance of transcriptional regulation and cell-cell signaling in Hox function. Four novel genes were also identified in the screen. One of these, rancor, is required for appropriate embryonic expression of Deformed and another homeotic gene, labial. Both Notch and nejire affect the function of another Hox gene, Ultrabithorax, indicating they may be required for homeotic activity in general.

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PICH, an ATP-dependent chromatin remodeling protein, transcriptionally co-regulates oxidative stress response.

10.1101/2021.07.21.453306 ◽

2021 ◽

Author(s):

Anindita Dutta ◽

Apurba Das ◽

Deep Bisht ◽

Vijendra Arya ◽

Rohini Muthuswami

Keyword(s):

Oxidative Stress ◽

Transcription Factor ◽

Transcriptional Regulation ◽

Stress Response ◽

Chromatin Remodeling ◽

Dna Sequences ◽

Target Genes ◽

Antioxidant Response ◽

Oxidative Stress Response ◽

Antioxidant Genes

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation often implemented by chromatin remodeling proteins. The study presented in this paper shows that the expression of PICH, an ATP-dependent chromatin remodeler, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response, both in the absence and presence of oxidative stress. In turn, Nrf2 regulates the expression of PICH in the presence of oxidative stress. Both PICH and Nrf2 together regulate the expression of antioxidant genes and this transcriptional regulation is dependent on the ATPase activity of PICH. In addition, H3K27ac modification also plays a role in activating transcription in the presence of oxidative stress. Co-immunoprecipitation experiments show that PICH and Nrf2 interact with H3K27ac in the presence of oxidative stress. Mechanistically, PICH recognizes ARE sequences present on its target genes and introduces a conformational change to the DNA sequences leading us to hypothesize that PICH regulates transcription by remodeling DNA. PICH ablation leads to reduced expression of Nrf2 and impaired antioxidant response leading to increased ROS content, thus, showing PICH is essential for the cell to respond to oxidative stress.

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Sox transcription factor mediated transcriptional regulation of Robo4 expression and function

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.9.3 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Ganesh Vinayak Samant ◽

Kallal Pramanik ◽

Noah Leigh ◽

Mark Horswill ◽

Monica Beltrame ◽

...

Keyword(s):

Transcription Factor ◽

Transcriptional Regulation ◽

And Function

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The ETS-Domain Transcription Factor Elk-1 Regulates COX-2 Gene Expression and Inhibits Glucose-Stimulated Insulin Secretion in the Pancreaticβ-Cell Line INS-1

International Journal of Endocrinology ◽

10.1155/2013/843462 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8

Author(s):

Xiong-Fei Zhang ◽

Yi Zhu ◽

Wen-Biao Liang ◽

Jing-Jing Zhang

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Regulation ◽

Insulin Secretion ◽

Cell Line ◽

Molecular Mechanisms ◽

Cell Function ◽

Cell Dysfunction ◽

Cox 2 ◽

Glucose Stimulated Insulin Secretion

Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreaticβ-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impairβ-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. We previously demonstrated that transcription factor Elk-1 significantly upregulated COX-2 gene promoter activity. In this report, we used pancreaticβ-cell line (INS-1) to explore the relationships between Elk-1 and COX-2. We first investigated the effects of Elk-1 on COX-2 transcriptional regulation and expression in INS-1 cells. We thus undertook to study the binding of Elk-1 to its putative binding sites in the COX-2 promoter. We also analysed glucose-stimulated insulin secretion (GSIS) in INS-1 cells that overexpressed Elk-1. Our results demonstrate that Elk-1 efficiently upregulates COX-2 expression at least partly through directly binding to the −82/−69 region of COX-2 promoter. Overexpression of Elk-1 inhibits GSIS in INS-1 cells. These findings will be helpful for better understanding the transcriptional regulation of COX-2 in pancreaticβ-cell. Moreover, Elk-1, the transcriptional regulator of COX-2 expression, will be a potential target for the prevention ofβ-cell dysfunction mediated by PGE2.

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Wild-Type Circadian Rhythmicity Is Dependent on Closely Spaced E Boxes in the Drosophila timelessPromoter

Molecular and Cellular Biology ◽

10.1128/mcb.21.4.1207-1217.2001 ◽

2001 ◽

Vol 21 (4) ◽

pp. 1207-1217 ◽

Cited By ~ 51

Author(s):

Michael J. McDonald ◽

Michael Rosbash ◽

Patrick Emery

Keyword(s):

Transcription Factor ◽

Transcriptional Regulation ◽

Locomotor Activity ◽

Circadian Rhythms ◽

High Amplitude ◽

Wild Type ◽

Activity Rhythms ◽

E Box ◽

E Boxes ◽

Circadian Transcription

ABSTRACT Transcriptional regulation plays an important role inDrosophila melanogaster circadian rhythms. The period promoter has been well studied, but the timeless promoter has not been analyzed in detail. Mutagenesis of the canonical E box in the timelesspromoter reduces but does not eliminate timeless mRNA cycling or locomotor activity rhythms. This is because there are at least two other cis-acting elements close to the canonical E box, which can also be transactivated by the circadian transcription factor dCLOCK. These E-box-like sequences cooperate with the canonical E-box element to promote high-amplitude transcription, which is necessary for wild-type rhythmicity.

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