Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor

ABSTRACT Yrr1p is a recently described Zn2Cys6 transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.

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Histone deacetylase 3 preferentially binds and collaborates with the transcription factor RUNX1 to repress AML1–ETO–dependent transcription in t(8;21) AML

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.010707 ◽

2020 ◽

Vol 295 (13) ◽

pp. 4212-4223 ◽

Cited By ~ 1

Author(s):

Chun Guo ◽

Jian Li ◽

Nickolas Steinauer ◽

Madeline Wong ◽

Brent Wu ◽

...

Keyword(s):

Transcription Factor ◽

Fusion Protein ◽

Histone Deacetylase ◽

Transcriptional Activation ◽

Target Genes ◽

Chromosomal Translocation ◽

Histone Deacetylase 3 ◽

Genome Wide ◽

Related Transcription Factor ◽

Almost All

In up to 15% of acute myeloid leukemias (AMLs), a recurring chromosomal translocation, termed t(8;21), generates the AML1–eight–twenty-one (ETO) leukemia fusion protein, which contains the DNA-binding domain of Runt-related transcription factor 1 (RUNX1) and almost all of ETO. RUNX1 and the AML1–ETO fusion protein are coexpressed in t(8;21) AML cells and antagonize each other's gene-regulatory functions. AML1–ETO represses transcription of RUNX1 target genes by competitively displacing RUNX1 and recruiting corepressors such as histone deacetylase 3 (HDAC3). Recent studies have shown that AML1–ETO and RUNX1 co-occupy the binding sites of AML1–ETO–activated genes. How this joined binding allows RUNX1 to antagonize AML1–ETO–mediated transcriptional activation is unclear. Here we show that RUNX1 functions as a bona fide repressor of transcription activated by AML1–ETO. Mechanistically, we show that RUNX1 is a component of the HDAC3 corepressor complex and that HDAC3 preferentially binds to RUNX1 rather than to AML1–ETO in t(8;21) AML cells. Studying the regulation of interleukin-8 (IL8), a newly identified AML1–ETO–activated gene, we demonstrate that RUNX1 and HDAC3 collaboratively repress AML1–ETO–dependent transcription, a finding further supported by results of genome-wide analyses of AML1–ETO–activated genes. These and other results from the genome-wide studies also have important implications for the mechanistic understanding of gene-specific coactivator and corepressor functions across the AML1–ETO/RUNX1 cistrome.

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Genome-wide identification of target genes repressed by the zinc finger transcription factor REST/NRSF in the HEK 293 cell line

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmp095 ◽

2009 ◽

Vol 41 (12) ◽

pp. 1008-1017 ◽

Cited By ~ 17

Author(s):

Z. Liu ◽

M. Liu ◽

G. Niu ◽

Y. Cheng ◽

J. Fei

Keyword(s):

Transcription Factor ◽

Cell Line ◽

Zinc Finger ◽

Target Genes ◽

Hek 293 ◽

Zinc Finger Transcription Factor ◽

Genome Wide ◽

Hek 293 Cell Line

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Genome-wide reduction in chromatin accessibility and unique transcription factor footprints in endothelial cells and fibroblasts in scleroderma skin

10.1101/2020.06.24.20138040 ◽

2020 ◽

Author(s):

Pei-Suen Tsou ◽

Pamela J. Palisoc ◽

Mustafa Ali ◽

Dinesh Khanna ◽

Amr H Sawalha

Keyword(s):

Endothelial Cells ◽

Transcription Factor ◽

Transcription Factors ◽

Target Genes ◽

Critical Role ◽

Vascular Complications ◽

Chromatin Accessibility ◽

Unknown Etiology ◽

Healthy Controls ◽

Genome Wide

AbstractSystemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by widespread fibrosis and vascular complications. We utilized an assay for genome-wide chromatin accessibility to examine the chromatin landscape and transcription factor footprints in both endothelial cells (ECs) and fibroblasts isolated from healthy controls and patients with diffuse cutaneous (dc) SSc. In both cell types, chromatin accessibility was significantly reduced in SSc patients compared to healthy controls. Genes annotated from differentially accessible chromatin regions were enriched in pathways and gene ontologies involved in the nervous system. In addition, our data revealed that chromatin binding of transcription factors SNAI2, ETV2, and ELF1 was significantly increased in dcSSc ECs, while recruitment of RUNX1 and RUNX2 was enriched in dcSSc fibroblasts. Significant elevation of SNAI2 and ETV2 levels in dcSSc ECs, and RUNX2 levels in dcSSc fibroblasts were confirmed. Further analysis of publicly available ETV2-target genes suggests that ETV2 may play a critical role in EC dysfunction in dcSSc. Our data, for the first time, uncovered the chromatin blueprint of dcSSc ECs and fibroblasts, and suggested that neural-related characteristics of SSc ECs and fibroblasts could be a culprit for dysregulated angiogenesis and enhanced fibrosis. Targeting these pathways and the key transcription factors identified might present novel therapeutic approaches for this disease.

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Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

10.1101/2020.06.16.155481 ◽

2020 ◽

Author(s):

Maud Fagny ◽

Marieke Lydia Kuijjer ◽

Maike Stam ◽

Johann Joets ◽

Olivier Turc ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Binding Sites ◽

Regulatory Network ◽

Tissue Specificity ◽

Target Genes ◽

Specific Gene ◽

Tissue Specific ◽

Genome Wide ◽

Gene Regulatory

AbstractEnhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity.SignificanceEnhancers play a major role in regulating tissue-specific gene expression in higher eukaryotes, including angiosperms. While molecular characterization of enhancers has improved over the past years, identifying their target genes at the genome-wide scale remains challenging. Here, we integrate genomic, epigenomic and transcriptomic data to decipher the tissue-specific gene regulatory network controlled by enhancers at two different stages of maize leaf development. Using a systems biology approach, we identify transcription factor families regulating gene tissue-specific expression in husk and seedling leaves, and characterize the enhancers likely to be involved. We show that a large part of maize enhancers is derived from transposable elements, which can provide novel transcription factor binding sites crucial to the regulation of tissue-specific biological functions.

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Hybrid allele-specific ChIP-Seq analysis links variation in transcription factor binding to traits in maize

10.21203/rs.3.rs-543958/v1 ◽

2021 ◽

Author(s):

Thomas Hartwig ◽

Michael Banf ◽

Gisele Prietsch ◽

Julia Engelhorn ◽

Jinliang Yang ◽

...

Keyword(s):

Transcription Factor ◽

Target Genes ◽

Phenotypic Diversity ◽

Association Studies ◽

Chromatin Accessibility ◽

Genome Wide Association Studies ◽

Functional Variants ◽

Genome Wide ◽

Allele Specific ◽

Hybrid Allele

Abstract Variation in transcriptional regulation is a major cause of phenotypic diversity. Genome-wide association studies (GWAS) have shown that most functional variants reside in non-coding regions, where they potentially affect transcription factor (TF) binding and chromatin accessibility to alter gene expression. Pinpointing such regulatory variations, however, remains challenging. Here, we developed a hybrid allele-specific chromatin binding sequencing (HASCh-seq) approach and identified variations in target binding of the brassinosteroid (BR) responsive transcription factor ZmBZR1 in maize. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) in B73xMo17 F1s identified thousands of target genes of ZmBZR1. Allele-specific ZmBZR1 binding (ASB) was observed for about 14.3% of target genes. It correlated with over 550 loci containing sequence variation in BZR1-binding motifs and over 340 loci with haplotype-specific DNA methylation, linking genetic and epigenetic variations to ZmBZR1 occupancy. Comparison with GWAS data linked hundreds of ASB loci to important yield, growth, and disease-related traits. Our study provides a robust method for analyzing genome-wide variations of transcription factor occupancy and identified genetic and epigenetic variations of the BR response transcription network in maize.

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Hepatocyte nuclear factor-1β regulates Wnt signaling through genome-wide competition with β-catenin/lymphoid enhancer binding factor

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1909452116 ◽

2019 ◽

Vol 116 (48) ◽

pp. 24133-24142 ◽

Cited By ~ 3

Author(s):

Siu Chiu Chan ◽

Ying Zhang ◽

Marco Pontoglio ◽

Peter Igarashi

Keyword(s):

Transcription Factor ◽

Wnt Signaling ◽

Target Genes ◽

Cystic Kidney ◽

Nuclear Factor ◽

Hepatocyte Nuclear Factor ◽

Wild Type ◽

Genome Wide ◽

Binding Factor ◽

Mutant Cells

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is essential for normal kidney development and renal tubular function. Mutations of HNF-1β produce cystic kidney disease, a phenotype associated with deregulation of canonical (β-catenin–dependent) Wnt signaling. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells produces hyperresponsiveness to Wnt ligands and increases expression of Wnt target genes, including Axin2, Ccdc80, and Rnf43. Levels of β-catenin and expression of Wnt target genes are also increased in HNF-1β mutant mouse kidneys. Genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) in wild-type and mutant cells showed that ablation of HNF-1β increases by 6-fold the number of sites on chromatin that are occupied by β-catenin. Remarkably, 50% of the sites that are occupied by β-catenin in HNF-1β mutant cells colocalize with HNF-1β–occupied sites in wild-type cells, indicating widespread reciprocal binding. We found that the Wnt target genes Ccdc80 and Rnf43 contain a composite DNA element comprising a β-catenin/lymphoid enhancer binding factor (LEF) site overlapping with an HNF-1β half-site. HNF-1β and β-catenin/LEF compete for binding to this element, and thereby HNF-1β inhibits β-catenin–dependent transcription. Collectively, these studies reveal a mechanism whereby a transcription factor constrains canonical Wnt signaling through direct inhibition of β-catenin/LEF chromatin binding.

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