The Drosophila Eip78C Gene Is Not Vital But Has a Role in Regulating Chromosome Puffs

Abstract We have generated a number of chromosomal aberrations that disrupt the early-late ecdysone-induced 78C puff gene (Eip78C, ecdysone-induced protein, FlyBase name for the E78 gene of Stone and Thummel 1993), which encodes the two members of the nuclear hormone receptor superfamily Eip78C-A and Eip78C-B. The aberrations include deletions of the ligand-binding/dimeriization domain of both, inversions that split Eip78C-A but retain residual Eip78C-B expression, and a small deletion specific for Eip78C-B. We find that wild-type Eip78C functions are completely dispensable for normal development under laboratory conditions. However, we show that Eip78C-B is required for the maximal puffing activity of a subset of late puffs (63E and 82F) since these puffs are reduced in size in Eip78C-B mutant backgrounds. Paradoxically the same late puffs are reduced, as well as at least one other, when the Eip78C-B cDNA is overexpressed from a heat shock promoter. These data indicate either that Eip78C function is redundant or that it plays a subtle modulating role in the regulation of chromosome puffing.

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Rhodopsin maturation antagonized by dominant rhodopsin mutants

Visual Neuroscience ◽

10.1017/s0952523898154093 ◽

1998 ◽

Vol 15 (4) ◽

pp. 693-700 ◽

Cited By ~ 21

Author(s):

PHANI KURADA ◽

TIMOTHY D. TONINI ◽

MICHELLE A. SERIKAKU ◽

JONATHAN P. PICCINI ◽

JOSEPH E. O'TOUSA

Keyword(s):

Heat Shock ◽

Vitamin A ◽

Visual Pigment ◽

Gene Activation ◽

Dominant Allele ◽

Wild Type ◽

Rhodopsin Gene ◽

Heat Shock Promoter ◽

Complex Forms

ninaED1, a dominant allele of the major Drosophila rhodopsin gene, expresses a rhodopsin that is predominantly recovered in a 80-kD complex that likely represents rhodopsin dimers. By driving either ninaED1 or ninaE+ expression from a heat-shock promoter, we show that the 80-kD rhodopsin complex forms immediately after gene activation. In wild type, but not ninaED1, rhodopsin monomeric forms are detected at later times. The generation of monomeric forms of wild-type rhodopsin is suppressed in vitamin A-deprived flies or in flies heterozygous for the dominant rhodopsin mutation. We also show that ninaED1 expression does not affect the maturation of another Drosophila visual pigment, Rh3. These results are consistent with the view that the ninaED1 rhodopsin antagonizes an early posttranslation process that is specific for maturation of the ninaE-encoded rhodopsin.

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Conserved nuclear receptors controlling a novel trait target fast-evolving genes expressed in a single cell

10.1101/809350 ◽

2019 ◽

Cited By ~ 1

Author(s):

Bogdan Sieriebriennikov ◽

Shuai Sun ◽

James W. Lightfoot ◽

Hanh Witte ◽

Eduardo Moreno ◽

...

Keyword(s):

Hormone Receptor ◽

Developmental Plasticity ◽

Genetic Basis ◽

Target Genes ◽

Gland Cell ◽

Nuclear Hormone Receptor ◽

Wild Type ◽

Phenotypic Effect ◽

Pharyngeal Gland ◽

Gene Regulatory

AbstractEnvironment shapes development through a phenomenon called developmental plasticity. Deciphering its genetic basis has implications for understanding evolution and adaptation to novel environments, yet molecular studies are scarce. Here, we expanded the gene regulatory network controlling predatory vs. non-predatory morphology in the nematode Pristionchus pacificus. First, we isolated a mutant in the nuclear hormone receptor nhr-1 with a previously unseen phenotypic effect. It disrupts mouth-form determination and results in animals combining features of both wild-type morphs. Further, we identified common targets of NHR-1 and the previously identified nuclear hormone receptor NHR-40 through transcriptomics. Unlike their highly conserved regulators, the target genes have no orthologs in Caenorhabditis elegans and likely result from lineage-specific expansions. An array of transcriptional reporters revealed co-expression of all tested targets in the same pharyngeal gland cell. The morphological remodeling of this cell accompanied the evolution of teeth and predation, linking rapid gene turnover with morphological innovations.

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The luteinizing hormone receptor: influence of buffer composition on ligand binding and signaling of wild type and mutant receptors

Molecular and Cellular Endocrinology ◽

10.1016/s0303-7207(03)00155-2 ◽

2003 ◽

Vol 204 (1-2) ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Krassimira Angelova ◽

Prema Narayan ◽

David Puett

Keyword(s):

Luteinizing Hormone ◽

Ligand Binding ◽

Hormone Receptor ◽

Luteinizing Hormone Receptor ◽

Wild Type ◽

Buffer Composition ◽

Mutant Receptors

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The Nuclear Hormone Receptor Coactivator NRC Is a Pleiotropic Modulator Affecting Growth, Development, Apoptosis, Reproduction, and Wound Repair

Molecular and Cellular Biology ◽

10.1128/mcb.24.11.4994-5004.2004 ◽

2004 ◽

Vol 24 (11) ◽

pp. 4994-5004 ◽

Cited By ~ 35

Author(s):

Muktar A. Mahajan ◽

Sharmistha Das ◽

Hong Zhu ◽

Marjana Tomic-Canic ◽

Herbert H. Samuels

Keyword(s):

Hormone Receptor ◽

Wound Repair ◽

Hormone Receptors ◽

Homozygous Deletion ◽

Nuclear Hormone Receptor ◽

High Rate ◽

Wild Type ◽

Postnatal Mortality ◽

Wild Type Mefs ◽

Interfering Rna

ABSTRACT Nuclear hormone receptor coregulator (NRC) is a 2,063-amino-acid coregulator of nuclear hormone receptors and other transcription factors (e.g., c-Fos, c-Jun, and NF-κB). We and others have generated C57BL/6-129S6 hybrid (C57/129) NRC+/− mice that appear outwardly normal and grow and reproduce. In contrast, homozygous deletion of the NRC gene is embryonic lethal. NRC−/− embryos are always smaller than NRC+/+ embryos, and NRC−/− embryos die between 8.5 and 12.5 days postcoitus (dpc), suggesting that NRC has a pleotrophic effect on growth. To study this, we derived mouse embryonic fibroblasts (MEFs) from 12.5-dpc embryos, which revealed that NRC−/− MEFs exhibit a high rate of apoptosis. Furthermore, a small interfering RNA that targets mouse NRC leads to enhanced apoptosis of wild-type MEFs. The finding that C57/129 NRC+/− mice exhibit no apparent phenotype prompted us to develop 129S6 NRC+/− mice, since the phenotype(s) of certain gene deletions may be strain dependent. In contrast with C57/129 NRC+/− females, 20% of 129S6 NRC+/− females are infertile while 80% are hypofertile. The 129S6 NRC+/− males produce offspring when crossed with wild-type 129S6 females, although fertility is reduced. The 129S6 NRC+/− mice tend to be stunted in their growth compared with their wild-type littermates and exhibit increased postnatal mortality. Lastly, both C57/129 NRC+/− and 129S6 NRC+/− mice exhibit a spontaneous wound healing defect, indicating that NRC plays an important role in that process. Our findings reveal that NRC is a coregulator that controls many cellular and physiologic processes ranging from growth and development to reproduction and wound repair.

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The Drosophila 78C early late puff contains E78, an ecdysone-inducible gene that encodes a novel member of the nuclear hormone receptor superfamily

Cell ◽

10.1016/0092-8674(93)80072-m ◽

1993 ◽

Vol 75 (2) ◽

pp. 307-320 ◽

Cited By ~ 67

Author(s):

Bryan L. Stone ◽

Carl S. Thummel

Keyword(s):

Hormone Receptor ◽

Nuclear Hormone Receptor ◽

Early Late ◽

Inducible Gene

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Atomistic simulations shed new light on the activation mechanisms of RORγ and classify it as Type III nuclear hormone receptor regarding ligand-binding paths

Scientific Reports ◽

10.1038/s41598-019-52319-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Suwipa Saen-Oon ◽

Estrella Lozoya ◽

Victor Segarra ◽

Victor Guallar ◽

Robert Soliva

Keyword(s):

Molecular Recognition ◽

Ligand Binding ◽

Hormone Receptor ◽

Nuclear Hormone Receptor ◽

Inverse Agonists ◽

Activator Proteins ◽

Type Iii ◽

Simulation Techniques ◽

Water Trapping

AbstractThe molecular recognition of the RORγ nuclear hormone receptor (NHR) ligand-binding domain (LBD) has been extensively studied with numerous X-ray crystal structures. However, the picture afforded by these complexes is static and does not fully explain the functional behavior of the LBD. In particular, the apo structure of the LBD seems to be in a fully active state, with no obvious differences to the agonist-bound structure. Further, several atypical in vivo inverse agonists have surprisingly been found to co-crystallize with the LBD in agonist mode (with co-activator), leading to a disconnection between molecular recognition and functional activity. Moreover, the experimental structures give no clues on how RORγ LBD binders access the interior of the LBD. To address all these points, we probe here, with a variety of simulation techniques, the fine structural balance of the RORγ LBD in its apo vs. holo form, the differences in flexibility and stability of the LBD in complex with agonists vs. inverse agonists and how binders diffuse in and out of the LBD in unbiased simulations. Our data conclusively point to the stability afforded by the so-called “agonist lock” between H479 and Y502 and the precise location of Helix 12 (H12) for the competence of the LBD to bind co-activator proteins. We observe the “water trapping” mechanism suggested previously for the atypical inverse agonists and discover a different behavior for the latter when co-activator is present or absent, which might help explain their conflicting data. Additionally, we unveil the same entry/exit path for agonists and inverse agonist into and out of the LBD for RORγ, suggesting it belongs to the type III NHR sub-family.

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Faculty Opinions recommendation of Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7660956.7972054 ◽

2011 ◽

Author(s):

Joel Elmquist ◽

Kevin Williams

Keyword(s):

Hormone Receptor ◽

Nuclear Hormone Receptor ◽

C Elegans ◽

Fat Uptake ◽

And Storage

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Distinct Modulation of Wild-Type and Selective Gene Mutated Vitamin D Receptor by Essential Poly Unsaturated Fatty Acids

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210104170408 ◽

2021 ◽

Vol 21 ◽

Author(s):

Hari Balaji ◽

Selvaraj Ayyamperuma ◽

Niladri Saha ◽

Shyam Sundar Pottabathula ◽

Jubie Selvaraj ◽

...

Keyword(s):

Fatty Acids ◽

Vitamin D ◽

Ligand Binding ◽

Vitamin D Deficiency ◽

Binding Affinity ◽

Unsaturated Fatty Acids ◽

Binding Domain ◽

Ligand Binding Domain ◽

Binding Energies ◽

Wild Type

: Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor’s (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of evidence report that selective long chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to transcriptional activation. We therefore hypothesize that selective PUFAs would modulate the dynamics and kinetics of VDRs, irrespective bioactive of vitamin-D binding. The spatial arrangements of the selected PUFAs in VDR active site were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR (PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.

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