scholarly journals Iron-Induced Dissociation of the Aft1p Transcriptional Regulator from Target Gene Promoters Is an Initial Event in Iron-Dependent Gene Suppression

2012 ◽  
Vol 32 (24) ◽  
pp. 4998-5008 ◽  
Author(s):  
R. Ueta ◽  
N. Fujiwara ◽  
K. Iwai ◽  
Y. Yamaguchi-Iwai
Keyword(s):  
Target Gene ◽  
Transcriptional Regulator ◽  
Gene Promoters ◽  
Gene Suppression ◽  
Initial Event

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 p53 dynamically directs TFIID assembly on target gene promoters

2016 ◽  
Author(s):  
R. A. Coleman ◽  
Z. Qiao ◽  
S. K. Singh ◽  
C. S. Peng ◽  
M. Cianfrocco ◽  
...  
Keyword(s):  
Dna Binding ◽  
Single Molecule ◽  
Transcription Initiation ◽  
Gene Networks ◽  
Target Gene ◽  
Core Promoter ◽  
Gene Promoters ◽  
Binding Modes ◽  
Dissociation Kinetics ◽  
Target Promoters

AbstractThe p53 tumor suppressor protein is a central regulator that turns on vast gene networks to maintain cellular integrity upon various stimuli. p53 activates transcription initiation in part by aiding recruitment of TFIID to the promoter. However, the precise means by which p53 dynamically interacts with TFIID to facilitate assembly on target gene promoters remains elusive. To address this key question, we have undertaken an integrated approach involving single molecule fluorescence microscopy, single particle cryo-electron microscopy, and biochemistry. Our real-time single molecule imaging demonstrates that TFIID alone binds poorly to native p53 target promoters. p53 unlocks TFIID’s ability to bind DNA by increasing TFIID contacts with both the core promoter and a region surrounding p53’s response element (RE). Analysis of single molecule dissociation kinetics reveals that TFIID interacts with promoters via transient and prolonged DNA binding modes that are each regulated by p53. Importantly, our structural work reveals that TFIID’s conversion from a canonical form to a rearranged DNA-binding conformation is enhanced in the presence of DNA and p53. Notably, TFIID’s interaction with DNA induces p53 to rapidly dissociate, effectively liberating the RE on the promoter. Collectively, these findings indicate that p53 dynamically escorts and loads the basal transcription machinery onto its target promoters.

scholarly journals Nuclear Hormone Receptors for Heme: REV-ERBα and REV-ERBβ Are Ligand-Regulated Components of the Mammalian Clock

2008 ◽  
Vol 22 (7) ◽  
pp. 1509-1520 ◽  
Author(s):  
Thomas P. Burris
Keyword(s):  
Nuclear Receptor ◽  
Cellular Differentiation ◽  
Target Gene ◽  
Hormone Receptors ◽  
Activation Function ◽  
Nuclear Hormone Receptors ◽  
Gene Promoters ◽  
Nuclear Receptor Corepressor ◽  
Small Molecule Ligands ◽  
Target Gene Transcription

Abstract The nuclear hormone receptors (NHRs), REV-ERBα and REV-ERBβ, regulate a number of physiological functions including the circadian rhythm, lipid metabolism, and cellular differentiation. These two receptors lack the activation function-2 region that is associated with the ability of NHRs to recruit coactivators and activate target gene transcription. These NHRs have been characterized as constitutive repressors of transcription due to their lack of an identified ligand and their strong ability to recruit the corepressor, nuclear receptor corepressor. Recently, the porphyrin heme was demonstrated to function as a ligand for both REV-ERBs. Heme binds directly to the ligand-binding domain and regulates the ability of these NHRs to recruit nuclear receptor corepressor to target gene promoters. This review focuses on the physiological roles that these two receptors play and the implications of heme functioning as their ligand. The prospect that these NHRs, now known to be regulated by small molecule ligands, may be targets for development of drugs for treatment of diseases associated with aberrant circadian rhythms including metabolic and psychiatric disorders as well as cancer is also addressed.

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 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.

Engineering of the LysR family transcriptional regulator FkbR1 and its target gene to improve ascomycin production

2017 ◽  
Vol 101 (11) ◽  
pp. 4581-4592 ◽  
Author(s):  
Kejing Song ◽  
Liang Wei ◽  
Jiao Liu ◽  
Junhua Wang ◽  
Haishan Qi ◽  
...  
Keyword(s):  
Target Gene ◽  
Transcriptional Regulator ◽  
Lysr Family
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