scholarly journals Coactivation of Estrogen Receptor β by Gonadotropin-Induced Cofactor GIOT-4

2008 ◽  
Vol 29 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Madoka Kouzu-Fujita ◽  
Yoshihiro Mezaki ◽  
Shun Sawatsubashi ◽  
Takahiro Matsumoto ◽  
Ikuko Yamaoka ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Gene Promoters ◽  
Ovulatory Cycle ◽  
Independent Manner ◽  
Ovarian Granulosa Cell ◽  
Transcriptional Regulatory Mechanism ◽  
Transcriptional Regulatory ◽  
Specific Stage ◽  
Regulatory Convergence

ABSTRACT Estrogen exerts its diverse effects through two subtypes of estrogen receptors (ER), ERα and ERβ. Each subtype has its own distinct function and expression pattern in its target tissues. Little, however, is known about the transcriptional regulatory mechanism of ERβ in the major ERβ-expressing tissues. Using biochemical methods, we identified and described a novel ERβ coactivator. This protein, designated GIOT-4, was biochemically purified from 293F cells. It coactivated ERβ in ovarian granulosa cells. GIOT-4 expression was induced by stimulation with follicle-stimulating hormone (FSH). GIOT-4 recruited an SWI/SNF-type complex in a ligand-independent manner to ERβ as an ER subtype-specific physical bridging factor and induced subsequent histone modifications in the ERβ target gene promoters in a human ovarian granulosa cell line (KGN). Indeed, two ERβ-specific target genes were upregulated by FSH at a specific stage of a normal ovulatory cycle in intact mice. These findings imply the presence of a novel regulatory convergence between the gonadotropin signaling cascade and ERβ-mediated transcription in the ovary.

scholarly journals Target Gene Specificity of E2F and Pocket Protein Family Members in Living Cells

2000 ◽  
Vol 20 (16) ◽  
pp. 5797-5807 ◽  
Author(s):  
Julie Wells ◽  
Kathryn E. Boyd ◽  
Christopher J. Fry ◽  
Stephanie M. Bartley ◽  
Peggy J. Farnham
Keyword(s):  
Cell Cycle ◽  
Target Gene ◽  
Target Genes ◽  
Protein Complexes ◽  
Current Model ◽  
Family Members ◽  
Living Cells ◽  
Gene Promoters ◽  
Pocket Protein ◽  
Protein Dna Interactions

ABSTRACT E2F-mediated transcription is thought to involve binding of an E2F-pocket protein complex to promoters in the G0 phase of the cell cycle and release of the pocket protein in late G1, followed by release of E2F in S phase. We have tested this model by monitoring protein-DNA interactions in living cells using a formaldehyde cross-linking and immunoprecipitation assay. We find that E2F target genes are bound by distinct E2F-pocket protein complexes which change as cells progress through the cell cycle. We also find that certain E2F target gene promoters are bound by pocket proteins when such promoters are transcriptionally active. Our data indicate that the current model applies only to certain E2F target genes and suggest that Rb family members may regulate transcription in both G0 and S phases. Finally, we find that a given promoter can be bound by one of several different E2F-pocket protein complexes at a given time in the cell cycle, suggesting that cell cycle-regulated transcription is a stochastic, not a predetermined, process.

scholarly journals Regulation of Poly(ADP-ribose) Polymerase-1-dependent Gene Expression through Promoter-directed Recruitment of a Nuclear NAD+ Synthase

2012 ◽  
Vol 287 (15) ◽  
pp. 12405-12416 ◽  
Author(s):  
Tong Zhang ◽  
Jhoanna G. Berrocal ◽  
Jie Yao ◽  
Michelle E. DuMond ◽  
Raga Krishnakumar ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Target Gene ◽  
Target Genes ◽  
Enzymatic Activities ◽  
Gene Promoters ◽  
Protein Coding ◽  
Photon Excitation ◽  
Gene Sets ◽  
Cellular Compartments ◽  
Parp 1

NMNAT-1 and PARP-1, two key enzymes in the NAD+ metabolic pathway, localize to the nucleus where integration of their enzymatic activities has the potential to control a variety of nuclear processes. Using a variety of biochemical, molecular, cell-based, and genomic assays, we show that NMNAT-1 and PARP-1 physically and functionally interact at target gene promoters in MCF-7 cells. Specifically, we show that PARP-1 recruits NMNAT-1 to promoters where it produces NAD+ to support PARP-1 catalytic activity, but also enhances the enzymatic activity of PARP-1 independently of NAD+ production. Furthermore, using two-photon excitation microscopy, we show that NMNAT-1 catalyzes the production of NAD+ in a nuclear pool that may be distinct from other cellular compartments. In expression microarray experiments, depletion of NMNAT-1 or PARP-1 alters the expression of about 200 protein-coding genes each, with about 10% overlap between the two gene sets. NMNAT-1 enzymatic activity is required for PARP-1-dependent poly(ADP-ribosyl)ation at the promoters of commonly regulated target genes, as well as the expression of those target genes. Collectively, our studies link the enzymatic activities of NMNAT-1 and PARP-1 to the regulation of a set of common target genes through functional interactions at target gene promoters.

scholarly journals Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program

2015 ◽  
Vol 112 (5) ◽  
pp. 1380-1385 ◽  
Author(s):  
Feng Zhang ◽  
Bogdan Tanasa ◽  
Daria Merkurjev ◽  
Chijen Lin ◽  
Xiaoyuan Song ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Binding Protein ◽  
Homeodomain Protein ◽  
Gene Promoters ◽  
Cell Type ◽  
Lim Domain ◽  
Transcriptional Initiation ◽  
Nucleosome Remodeling ◽  
Enhancer Binding Protein

Substantial evidence supports the hypothesis that enhancers are critical regulators of cell-type determination, orchestrating both positive and negative transcriptional programs; however, the basic mechanisms by which enhancers orchestrate interactions with cognate promoters during activation and repression events remain incompletely understood. Here we report the required actions of LIM domain-binding protein 1 (LDB1)/cofactor of LIM homeodomain protein 2/nuclear LIM interactor, interacting with the enhancer-binding protein achaete-scute complex homolog 1, to mediate looping to target gene promoters and target gene regulation in corticotrope cells. LDB1-mediated enhancer:promoter looping appears to be required for both activation and repression of these target genes. Although LDB1-dependent activated genes are regulated at the level of transcriptional initiation, the LDB1-dependent repressed transcription units appear to be regulated primarily at the level of promoter pausing, with LDB1 regulating recruitment of metastasis-associated 1 family, member 2, a component of the nucleosome remodeling deacetylase complex, on these negative enhancers, required for the repressive enhancer function. These results indicate that LDB1-dependent looping events can deliver repressive cargo to cognate promoters to mediate promoter pausing events in a pituitary cell type.

scholarly journals The Estrogen Receptor β-Isoform (ERβ) of the Human Estrogen Receptor Modulates ERα Transcriptional Activity and Is a Key Regulator of the Cellular Response to Estrogens and Antiestrogens1

Endocrinology ◽  
1999 ◽  
Vol 140 (12) ◽  
pp. 5566-5578 ◽  
Author(s):  
Julie M. Hall ◽  
Donald P. McDonnell
Keyword(s):  
Estrogen Receptor ◽  
Cellular Response ◽  
Transcriptional Activity ◽  
Target Gene ◽  
Partial Agonist ◽  
Target Cells ◽  
Gene Promoters ◽  
Independent Manner ◽  
Amino Acid Homology ◽  
Human Estrogen Receptor

Abstract The human estrogen receptor α (ERα) and the recently identified ERβ share a high degree of amino acid homology; however, there are significant differences in regions of these receptors that would be expected to influence transcriptional activity. Consequently, we compared the mechanism(s) by which these receptors regulate target gene transcription, and evaluated the cellular consequences of coexpression of both ER subtypes. Previously, it has been determined that ERα contains two distinct activation domains, ERα-AF-1 and ERα-AF-2, whose transcriptional activity is influenced by cell and promoter context. We determined that ERβ, like ERα, contains a functional AF-2, however, the ERβ-AF-2 domain functions independently within the receptor. Of additional significance was the finding that ERβ does not contain a strong AF-1 within its amino-terminus but, rather, contains a repressor domain that when removed, increases the overall transcriptional activity of the receptor. The importance of these findings was revealed when it was determined that ERβ functions as a transdominant inhibitor of ERα transcriptional activity at subsaturating hormone levels and that ERβ decreases overall cellular sensitivity to estradiol. Additionally, the partial agonist activity of tamoxifen manifest through ERα in some contexts was completely abolished upon coexpression of ERβ. In probing the mechanisms underlying ERβ-mediated repression of ERα transcriptional activity we have determined that 1) ERα and ERβ can form heterodimers within target cells; and 2) ERβ interacts with target gene promoters in a ligand-independent manner. Cumulatively, these data indicate that one role of ERβ is to modulate ERα transcriptional activity, and thus the relative expression level of the two isoforms will be a key determinant of cellular responses to agonists and antagonists.

scholarly journals Liver X Receptor Ligands Suppress Ubiquitination and Degradation of LXRα by Displacing BARD1/BRCA1

2009 ◽  
Vol 23 (4) ◽  
pp. 466-474 ◽  
Author(s):  
Kang Ho Kim ◽  
Jeong Min Yoon ◽  
A Hyun Choi ◽  
Woo Sik Kim ◽  
Gha Young Lee ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Target Gene ◽  
Target Genes ◽  
Cancer Susceptibility ◽  
Liver X Receptor ◽  
Lipid Homeostasis ◽  
Gene Promoters ◽  
Receptor Ligands ◽  
Ubiquitin E3 Ligase ◽  
Ligand Free

Abstract Liver X receptor (LXR) is a ligand-activated transcription factor that plays important roles in cholesterol and lipid homeostasis. However, ligand-induced posttranslational modification of LXR is largely unknown. Here, we show that ligand-free LXRα is rapidly degraded by ubiquitination. Without ligand, LXRα interacts with an ubiquitin E3-ligase protein complex containing breast and ovarian cancer susceptibility 1 (BRCA1)-associated RING domain 1 (BARD1). Interestingly, LXR ligand represses ubiquitination and degradation of LXRα, and the interaction between LXRα and BARD1 is inhibited by LXR ligand. Consistently, T0901317, a synthetic LXR ligand, increased the level of LXRα protein in liver. Moreover, overexpression of BARD1/BRCA1 promoted the ubiquitination of LXRα and reduced the recruitment of LXRα to the target gene promoters, whereas BARD1 knockdown reversed such effects. Taken together, these data suggest that LXR ligand prevents LXRα from ubiquitination and degradation by detaching BARD1/BRCA1, which might be critical for the early step of transcriptional activation of ligand-stimulated LXRα through a stable binding of LXRα to the promoters of target genes.

scholarly journals Unusual DNA-binding properties of the Arabidopsis thaliana WRKY50 transcription factor at target gene promoters

2020 ◽  
Author(s):  
Konstantin Kanofsky ◽  
Jendrik Rusche ◽  
Lea Eilert ◽  
Fabian Machens ◽  
Reinhard Hehl
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Target Gene ◽  
Target Genes ◽  
Specific Binding ◽  
Gene Promoters ◽  
Molecular Pattern ◽  
High Flexibility ◽  
Site Recognition

Abstract Key message WRKY50 from A. thaliana requires WT-boxes at target gene promoters for activation and binding. Abstract Based on the genome-wide prediction of WRKY50 target genes and the similarity of a WRKY50 binding site to WT-boxes in microbe-associated molecular pattern (MAMP)-responsive cis-regulatory modules (CRM), four WT-box containing CRMs from the promoter region of three WRKY50 target genes were investigated for their interaction with WRKY50. These target genes are DJ1E, WRKY30 and ATBBE4. Two of the four CRMs, one from DJ1E and one from WRKY30, were able to activate reporter gene expression in the presence of WRKY50. Activation requires the WT-boxes GGACTTTT, GGACTTTG from DJ1E and GGACTTTC from WRKY30. WRKY50 does not activate a second CRM from WRKY30 and the CRM from ATBBE4, both containing the WT-box TGACTTTT. In vitro gel-shift assays demonstrate WT-box-specific binding of the WRKY50 DNA-binding domain to all four CRMs. This work shows a high flexibility of WRKY50 binding site recognition beyond the classic W-box TTGACC/T.

scholarly journals MED14 Tethers Mediator to the N-Terminal Domain of Peroxisome Proliferator-Activated Receptor γ and Is Required for Full Transcriptional Activity and Adipogenesis

2010 ◽  
Vol 30 (9) ◽  
pp. 2155-2169 ◽  
Author(s):  
Lars Grøntved ◽  
Maria S. Madsen ◽  
Michael Boergesen ◽  
Robert G. Roeder ◽  
Susanne Mandrup
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activity ◽  
Target Gene ◽  
Target Genes ◽  
Gene Activation ◽  
Proximal Promoter ◽  
Peroxisome Proliferator ◽  
Independent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Terminal Domain

ABSTRACT The Mediator subunit MED1/TRAP220/DRIP205/PBP interacts directly with many nuclear receptors and was long thought to be responsible for tethering Mediator to peroxisome proliferator-activated receptor (PPAR)-responsive promoters. However, it was demonstrated recently that PPARγ can recruit Mediator by MED1-independent mechanisms. Here, we show that target gene activation by ectopically expressed PPARγ and PPARα is independent of MED1. Consistent with this finding, recruitment of PPARγ, MED6, MED8, TATA box-binding protein (TBP), and RNA polymerase II (RNAPII) to the enhancer and proximal promoter of the PPARγ target gene Fabp4 is also independent of MED1. Using a small interfering RNA (siRNA)-based approach, we identify MED14 as a novel critical Mediator component for PPARγ-dependent transactivation, and we demonstrate that MED14 interacts directly with the N terminus of PPARγ in a ligand-independent manner. Interestingly, MED14 knockdown does not affect the recruitment of PPARγ, MED6, and MED8 to the Fabp4 enhancer but does reduce their occupancy of the Fabp4 proximal promoter. In agreement with the necessity of MED14 for PPARγ transcriptional activity, we show that knockdown of MED14 impairs adipogenesis of 3T3-L1 cells. Thus, MED14 constitutes a novel anchoring point between Mediator and the N-terminal domain of PPARγ that is necessary for functional PPARγ-mediated recruitment of Mediator and transactivation of PPARγ subtype-specific target genes.

scholarly journals Genome-wide comprehensive analysis of miRNAs and their target genes expressed in resistant and susceptible Capsicum annuum landrace during Phytophthora capsici infection

2021 ◽  
Author(s):  
Tilahun Rabuma ◽  
Om Prakash Gupta ◽  
Vinod Chhokar
Keyword(s):  
Capsicum Annuum ◽  
Target Genes ◽  
Phytophthora Capsici ◽  
Chilli Pepper ◽  
Accumulation Pattern ◽  
Disease Response ◽  
Genome Wide ◽  
Transcriptional Regulatory Mechanism ◽  
Transcriptional Regulatory ◽  
Small Rna Deep Sequencing

AbstractMiRNAs regulate plants responses to fungal infection and immunity by modulating the gene expression. Despite extensive works on miRNA’s role during plant-fungus interaction, work in Capsicum annuum-Phytophthora capsici pathosystem is limited. Therefore, in the current study, genome-wide known and novel miRNAs were identified in two contrasting chilli pepper landraces, i.e. GojamMecha_9086 (resistant) and Dabat_80045 (susceptible) during P. capsici infection. The small RNA deep sequencing resulted in 79 known miRNAs corresponding to 24 miRNAs families and 477 novel miRNAs along with 22,895 potential targets, including 30 defence-related genes against P. capsici infection. The expression analysis of ∼29 known & 157 novel miRNAs in resistant and 30 known and 176 novel miRNAs in susceptible landrace revealed differential accumulation pattern. RT-qPCR of a set of 8 defence related miRNAs representing 4 novel (Pz-novel-miR428-1, Pz-novel-miR160-1, Pz-novel-miR1028-1, Pz-novel-miR204-1) and 4 known (Pz-known-miR803-1, Pz-known-miR2059-1, Pz-known-miR2560-1, Pz-known-miR1872-1) revealed differential accumulation pattern in both resistant and susceptible landrace. Additionally, validation of 8 target genes of corresponding miRNAs using RA-PCR, which as good as 5’ RLM-RACE, revealed an inverse relation with their corresponding miRNAs suggesting their key role during disease response. This study provides comprehensive genome-wide information about the repertoire of miRNAs and their target genes expressed in resistant and susceptible chilli pepper landrace, which can serve as a valuable resource for better understanding the post-transcriptional regulatory mechanism during C. annuum - P. capsici pathosystem.

Histone Deacetylase 3 (HDAC3), a Component of N-CoR-TBL1/R1 Chromatin Remodeling Co-Repressor Complex, Is Recruited to the Target Gene Promoters by PML-RARα To Repress the Transcription In Vivo.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2750-2750
Author(s):  
Akihiro Tomita ◽  
Akihide Atsumi ◽  
Hitoshi Kiyoi ◽  
Tomoki Naoe
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Target Gene ◽  
Target Genes ◽  
Gene Promoters ◽  
Transcription Repression ◽  
Histone Deacetylase 3 ◽  
Repressor Complex ◽  
Endogenous Target

Abstract PML-RARα is a chimeric transcription factor deeply associated with acute promyelocytic leukemia (APL). PML-RARα plays an important role in the aberrant transcription repression on the target genes of wild type retinoic acid receptors (RARα). Pharmacological concentration of all-trans retinoic acid (ATRA) induces transcription de-repression on several target genes, and results in terminal differentiation of APL cells. However, the detailed mechanisms of transcription repression by PML-RARα in vivo are still unclear. Here we demonstrated that histone deacetylase 3 (HDAC3), one component of the N-CoR (nuclear receptor co-repressor)-TBL1/R1 (transducin beta-like protein 1/relating protein) transcription repressor protein complex, is a key regulator of the transcription repression by PML-RARα in vivo. Using immunoprecipitation (IP) assay, we first demonstrated that PML-RARα physically interacted with N-CoR/HDAC3 in vivo in the absence of ligand. The interaction was dissociated by adding ATRA in the dose dependent manner. Next we showed, using chromatin immunoprecipitation (ChIP) assay, that N-CoR/HDAC3 co-repressor complex was recruited to the endogenous target gene promoters (RARβ and CYP26) through PML-RARα. The neighboring histone H4 was de-acetylated and the gene expression was significantly repressed. When HDAC3 protein is knocked down by RNA interference in PML-RARα-presenting cells, the endogenous target gene expression was significantly activated. Almost the same results were also obtained when performing the luciferase reporter assay using RARβ and CYP26 promoter reporter vectors. Previously, we have shown that N-CoR-TBLR1 is recruited to the target gene promoter through PML-RARα in the absence of ligand, resulting in the transcription repression. Consistent with these data, it is strongly suggested that N-CoR/HDAC3/TBLR1 co-repressor complex is closely related to the aberrant transcription regulation by PML-RARα in APL cells. Furthermore, we also confirmed that PLZF-RARα, which is expressed in ATRA resistant APL cells, interacted with N-CoR/HDAC3/TBLR1 in ligand independent manner. These insights provide not only the basic mechanism of transcription repression by leukemia-related chimeric transcription factors, but also the new molecular targets for the transcription therapy for leukemia.

scholarly journals The ING4 Tumor Suppressor Attenuates NF-κB Activity at the Promoters of Target Genes

2008 ◽  
Vol 28 (21) ◽  
pp. 6632-6645 ◽  
Author(s):  
Susan Nozell ◽  
Travis Laver ◽  
Dorothy Moseley ◽  
Lisa Nowoslawski ◽  
Marijke DeVos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor ◽  
Target Gene ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Gene Promoters ◽  
Protein Levels ◽  
Expression Of Genes ◽  
Regulated Gene Expression

ABSTRACT The NF-κB family mediates immune and inflammatory responses. In many cancers, NF-κB is constitutively activated and induces the expression of genes that facilitate tumorigenesis. ING4 is a tumor suppressor that is absent or mutated in several cancers. Herein, we demonstrate that in human gliomas, NF-κB is constitutively activated, ING4 expression is negligible, and NF-κB-regulated gene expression is elevated. We demonstrate that an ING4 and NF-κB interaction exists but does not prevent NF-κB activation, nuclear translocation, or DNA binding. Instead, ING4 and NF-κB bind simultaneously at NF-κB-regulated promoters, and this binding correlates with reductions in p65 phosphorylation, p300, and the levels of acetylated histones and H3-Me3K4, while enhancing the levels of HDAC-1 at these promoters. Using a knockdown approach, we correlate reductions in ING4 protein levels with increased basal and inducible NF-κB target gene expression. Collectively, these data suggest that ING4 may specifically regulate the activity of NF-κB molecules that are bound to target gene promoters.

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