Identification of two independent nucleosome-binding domains in the transcriptional co-activator SPBP

2012 ◽  
Vol 442 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Sagar Darvekar ◽  
Sylvia Sagen Johnsen ◽  
Agnete Bratsberg Eriksen ◽  
Terje Johansen ◽  
Eva Sjøttem
Keyword(s):  
Transcription Factors ◽  
Dependent Manner ◽  
Chromatin Binding ◽  
Binding Region ◽  
Interaction Domain ◽  
Binding Domains ◽  
Element Binding Protein ◽  
Inducible Protein ◽  
Responsive Element ◽  
Nucleosome Binding

Transcriptional regulation requires co-ordinated action of transcription factors, co-activator complexes and general transcription factors to access specific loci in the dense chromatin structure. In the present study we demonstrate that the transcriptional co-regulator SPBP [stromelysin-1 PDGF (platelet-derived growth factor)-responsive element binding protein] contains two independent chromatin-binding domains, the SPBP-(1551–1666) region and the C-terminal extended PHD [ePHD/ADD (extended plant homeodomain/ATRX-DNMT3-DNMT3L)] domain. The region 1551–1666 is a novel core nucleosome-interaction domain located adjacent to the AT-hook motif in the DNA-binding domain. This novel nucleosome-binding region is critically important for proper localization of SPBP in the cell nucleus. The ePHD/ADD domain associates with nucleosomes in a histone tail-dependent manner, and has significant impact on the dynamic interaction between SPBP and chromatin. Furthermore, SPBP and its homologue RAI1 (retinoic-acid-inducible protein 1), are strongly enriched on chromatin in interphase HeLa cells, and both proteins display low nuclear mobility. RAI1 contains a region with homology to the novel nucleosome-binding region SPBP-(1551–1666) and an ePHD/ADD domain with ability to bind nucleosomes. These results indicate that the transcriptional co-regulator SPBP and its homologue RAI1 implicated in Smith–Magenis syndrome and Potocki–Lupski syndrome both belong to the expanding family of chromatin-binding proteins containing several domains involved in specific chromatin interactions.

scholarly journals cAMP-responsive element-binding protein expression and regulation in the mouse preimplantation embryo

Reproduction ◽  
2007 ◽  
Vol 134 (5) ◽  
pp. 667-675 ◽  
Author(s):  
X L Jin ◽  
C O’Neill
Keyword(s):  
Transcription Factors ◽  
Preimplantation Embryo ◽  
Binding Protein ◽  
Dependent Manner ◽  
Cell Stage ◽  
Embryonic Genome ◽  
Element Binding Protein ◽  
Cell Embryo ◽  
Responsive Element ◽  
Camp Responsive Element Binding

Gene expression from the new embryonic genome is required for normal preimplantation embryo development. Two members of the cAMP-responsive element-binding protein (Creb) family of transcription factors, Creb1 and activating transcription factor 1 (Atf1), are essential for normal preimplantation development. These transcription factors are activated by phosphorylation. Creb1 mRNA was expressed throughout the preimplantation phase. Cytoplasmic immunolocalization of Creb1 was detected in all preimplantation embryo stages. The antigen was largely excluded from the pronuclei/nuclei at embryonic stages except in the mid-cycle two-cell and compacted eight-cell embryo. Activation-state-specific antibodies showed serine 133 phosphorylated Creb1 localization was similar to Creb1 staining, except that there was no increase in staining at the eight-cell stage. Increased staining of phosphorylated Creb1 was observed in the nucleus of mid-cycle two-cell embryos. Increased expression of phosphorylated Creb1 in the two-cell embryo was induced by brief exposure of embryos to ionomycin, but not by a dibutyryl cAMP. This was blocked by buffering intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester), but not by a cAMP antagonist, Rp-cyclic 3′,5′-hydrogen phosphorothioate adenosine. Calmodulin is an intracellular receptor for calcium. Calmodulin mRNA was expressed throughout the preimplantation phase of development. The calmodulin antagonist, W-7, inhibited the ionomycin-induced localization of phosphorylated Creb1 in the nucleus. Treatment of embryos with W-7 caused a dose-dependent inhibition of normal development of zygotes to the blastocysts stage. The study shows Creb1 expression and nuclear localization was dynamically regulated in the early embryo. The marked nuclear accumulation and phosphorylation of Creb1 at the two-cell stage occurred at the time of transcription from the embryonic genome and was regulated in a calcium- and calmodulin-dependent manner.

scholarly journals cAMP-Responsive Element Binding Protein: A Vital Link in Embryonic Hormonal Adaptation

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2208-2221 ◽  
Author(s):  
Maria Schindler ◽  
Sünje Fischer ◽  
René Thieme ◽  
Bernd Fischer ◽  
Anne Navarrete Santos
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Binding Protein ◽  
Cell Lineage ◽  
Element Binding Protein ◽  
A Cell ◽  
Responsive Element ◽  
Camp Responsive Element Binding

Abstract The transcription factor cAMP responsive element-binding protein (CREB) and activating transcription factors (ATFs) are downstream components of the insulin/IGF cascade, playing crucial roles in maintaining cell viability and embryo survival. One of the CREB target genes is adiponectin, which acts synergistically with insulin. We have studied the CREB-ATF-adiponectin network in rabbit preimplantation development in vivo and in vitro. From the blastocyst stage onwards, CREB and ATF1, ATF3, and ATF4 are present with increasing expression for CREB, ATF1, and ATF3 during gastrulation and with a dominant expression in the embryoblast (EB). In vitro stimulation with insulin and IGF-I reduced CREB and ATF1 transcripts by approximately 50%, whereas CREB phosphorylation was increased. Activation of CREB was accompanied by subsequent reduction in adiponectin and adiponectin receptor (adipoR)1 expression. Under in vivo conditions of diabetes type 1, maternal adiponectin levels were up-regulated in serum and endometrium. Embryonic CREB expression was altered in a cell lineage-specific pattern. Although in EB cells CREB localization did not change, it was translocated from the nucleus into the cytosol in trophoblast (TB) cells. In TB, adiponectin expression was increased (diabetic 427.8 ± 59.3 pg/mL vs normoinsulinaemic 143.9 ± 26.5 pg/mL), whereas it was no longer measureable in the EB. Analysis of embryonic adipoRs showed an increased expression of adipoR1 and no changes in adipoR2 transcription. We conclude that the transcription factors CREB and ATFs vitally participate in embryo-maternal cross talk before implantation in a cell lineage-specific manner. Embryonic CREB/ATFs act as insulin/IGF sensors. Lack of insulin is compensated by a CREB-mediated adiponectin expression, which may maintain glucose uptake in blastocysts grown in diabetic mothers.

scholarly journals Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2254
Author(s):  
Mohammed Shariful Azam ◽  
Bonggi Lee ◽  
Jae-Il Kim ◽  
Chang Geun Choi ◽  
Jinkyung Choi ◽  
...  
Keyword(s):  
Docking Simulation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Regulatory Subunit ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Creb Activation ◽  
B16f10 Cells ◽  
Element Binding Protein ◽  
Responsive Element

Hyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melanin content in a concentration-dependent manner and attenuated the expression of TYR and tyrosinase-related protein 1 (TRP1), along with their transcriptional regulator, microphthalmia-associated transcription factor (MITF). SHQA also suppressed α-MSH-induced cellular production of cyclic adenosine monophosphate (cAMP), which inhibited protein kinase A (PKA)-dependent cAMP-responsive element-binding protein (CREB) activation. Docking simulation data showed a potential binding affinity of SHQA to the regulatory subunit RIIβ of PKA, which may also adversely affect PKA and CREB activation. Moreover, SHQA activated ERK1/2 signaling in B16F10 cells, stimulating the proteasomal degradation of MITF. These data suggest that SHQA ameliorated hyperpigmentation in α-MSH-stimulated B16F10 cells by downregulating MITF via PKA inactivation and ERK1/2 phosphorylation, indicating that SHQA is a potent therapeutic agent against skin hyperpigmentation disorders.

scholarly journals SPBP Is a Phosphoserine-Specific Repressor of Estrogen Receptor α

2005 ◽  
Vol 25 (9) ◽  
pp. 3421-3430 ◽  
Author(s):  
Valentina Gburcik ◽  
Nathalie Bot ◽  
Marcello Maggiolini ◽  
Didier Picard
Keyword(s):  
Estrogen Receptor ◽  
Activation Function ◽  
Estrogen Receptor Α ◽  
Fine Tuning ◽  
Breast Cancer Cell Lines ◽  
Interaction Domain ◽  
Phosphorylated Form ◽  
Element Binding Protein ◽  
Responsive Element

ABSTRACT Multiple signaling pathways stimulate the activity of estrogen receptor α (ERα) by direct phosphorylation within its N-terminal activation function 1 (AF1). How phosphorylation affects AF1 activity remains poorly understood. We performed a phage display screen for human proteins that are exclusively recruited to the phosphorylated form of AF1 and found the stromelysin-1 platelet-derived growth factor-responsive element-binding protein (SPBP). In a purified system, SPBP bound only the in vitro-phosphorylated form of the ERα AF1 or the phosphoserine mimic S118E, and the interaction domain could be mapped to a 42-amino-acid fragment of SPBP. In cells, SPBP preferentially interacted with liganded and phosphorylated ERα. Functionally, SPBP behaved as a repressor of activated ERα, which extends its previously demonstrated roles as a DNA binding transactivation factor and coactivator of other transcription factors. By targeting the phosphorylated form of AF1, SPBP may contribute to attenuating and fine-tuning ERα activity. A functional consequence is that SPBP inhibits the proliferation of ERα-dependent but not ERα-independent breast cancer cell lines, mirroring a reported negative correlation with the ERα status of breast tumors.

scholarly journals Functional Analysis of Two Zinc (Zn) Transporters (ZIP3 and ZIP8) Promoters and Their Distinct Response to MTF1 and RREB1 in the Regulation of Zn Metabolism

2020 ◽  
Vol 21 (17) ◽  
pp. 6135
Author(s):  
Shu-Wei Chen ◽  
Kun Wu ◽  
Wu-Hong Lv ◽  
Fang Chen ◽  
Chang-Chun Song ◽  
...  
Keyword(s):  
Binding Site ◽  
Luciferase Activity ◽  
Binding Protein ◽  
Pelteobagrus Fulvidraco ◽  
Dependent Manner ◽  
Promoter Regions ◽  
Functional Sites ◽  
Zip Family ◽  
Element Binding Protein ◽  
Responsive Element

ZIP (zinc-regulated transporters, iron-regulated transporter-like protein) family plays an important role in organism Zn balance. This research identified the promoter regions of ZIP3 and ZIP8, two members of ZIP family, from a freshwater teleost yellow catfish Pelteobagrus fulvidraco, characterized the binding sequences of the metal-responsive transcription factor-1 (MTF-1) and Ras responsive element binding protein 1 (RREB1) on their promoter regions. The present study cloned and obtained the 2027 bp of ZIP3 promoter and 1664 bp of ZIP8 promoter, and predicted several key elements on their promoters, such as the binding sites of CREB (cAMP-response element binding protein), KLF4 (Kruppel like factor 4), MTF-1 and RREB1. The sequence deletion from −361 bp to −895 bp down-regulated the luciferase activity of ZIP3 promoter, and the deletion from −897 bp to −1664 bp down-regulated the luciferase activity of ZIP8 promoter. Within different deletion plasmids, the relative luciferase activities of ZIP3 and ZIP8 promoters changes to Zn incubation in a Zn concentration-dependent manner. The site mutagenesis and EMSA (electrophoretic mobility shift assay) found that the −1327 bp/−1343 bp MTF-1 binding site and the −248 bp/−267 bp RREB1 binding site on the ZIP3 promoter, and the −1543 bp/−1557 bp MTF-1 binding site on the ZIP8 promoter are functional sites. Low Zn increased the binding capability between MTF-1 and its responsive site on the ZIP3 promoter, and high Zn increased the transcriptional activation ZIP3 by RREB1; Zn also promoted the binding ability between MTF-1 and its responsive element on the ZIP8 promoter. This study provides the first direct evidence for the response elements of MTF-1 and RREB1 on ZIP3 and MTF-1 on ZIP8 to Zn, which are very important for the evaluation of Zn nutrition and toxicity in vertebrates.

Transcription factors acting on the promoter of the rat fatty acid synthase gene

2002 ◽  
Vol 30 (6) ◽  
pp. 1070-1072 ◽  
Author(s):  
M. Schweizer ◽  
K. Roder ◽  
L. Zhang ◽  
S. S. Wolf
Keyword(s):  
Transcription Factors ◽  
Fatty Acid ◽  
Binding Sites ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Upstream Stimulatory Factor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Responsive Element ◽  
Stimulatory Factor

Fatty acid synthase (FAS), one of the main lipogenic enzymes, converts dietary calories into a storage form of energy. The transcription factors, stimulatory proteins 1 and 3 (Sp1 and Sp3), nuclear factor Y (NF-Y), upstream stimulatory factor (USF) and sterol regulatory element binding protein-1 (SREBP-1) have cognate binding sites on the promoter of the FAS gene. It was shown that Sp1 and NF-Y interact co-operatively at the diet-induced DNase I-hypersensitive site at position —500. Adjacent binding sites for NF-Y and Sp1 have also been found between —71 and —52, and —91 and —83. cAMP regulation is mediated via the inverted CAAT element (ICE) at —99 to —92, which binds NF-Y. The FAS insulin-responsive element 3 (FIRE3)-binding site at —71 to —52 is capable of binding NF-Y, USF and SREBP-1, and is required for the sterol response in conjunction with the co-activator NF-Y around —100. Surprisingly, both FIRE3 and ICE are also necessary for the response to retinoic acid that plays a role in development and is an essential component of the diet.

scholarly journals Variable Expression of the Transcription Factors cAMP Response Element-Binding Protein and Inducible cAMP Early Repressor in the Normal Adrenal Cortex and in Adrenocortical Adenomas and Carcinomas

2001 ◽  
Vol 86 (11) ◽  
pp. 5443-5449 ◽  
Author(s):  
Alessandro Peri ◽  
Paola Luciani ◽  
Barbara Conforti ◽  
Silvana Baglioni-Peri ◽  
Federica Cioppi ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Adrenal Cortex ◽  
Binding Protein ◽  
Telomerase Activity ◽  
Steroid Synthesis ◽  
Inducible Camp Early Repressor ◽  
Adrenocortical Adenomas ◽  
Acth Receptor ◽  
Element Binding Protein ◽  
Responsive Element

The molecular mechanisms leading to adrenocortical tumorigenesis have been only partially elucidated so far. Because the pituitary hormone ACTH, via activation of the cAMP pathway, regulates both cell proliferation/differentiation and steroid synthesis in the adrenal cortex, in this study we focused on the cAMP-dependent transcription factors cAMP responsive element modulator (CREM) and cAMP responsive element binding protein (CREB). We studied CREM and CREB expression by RT-PCR in human normal adrenal cortex (n = 3), adrenocortical adenomas (n = 8), and carcinomas (n = 8). We found transcripts corresponding to the isoforms α, β, γ, and τ2 of the CREM gene in all of the normal adrenal tissues, in the adenomas, and in seven of eight carcinomas. On the other hand, mRNA for the inducible cAMP early repressor isoforms, which derive from an internal promoter of CREM gene, was detected in the normal adrenal and in seven of eight adenomas, but in only three of eight carcinomas. Similarly, CREB transcripts were readily detectable in all normal adrenals and adenomas, whereas they were not found in four of eight adrenal carcinomas. To further characterize the carcinomas, telomerase activity and the expression of the ACTH receptor gene were determined. Telomerase activity in the carcinomas resulted in levels significantly higher than in the adenomas, whereas the levels of ACTH receptor mRNA were lower in the carcinomas. No correlation was found in the carcinomas between the levels of the ACTH receptor transcript and the loss of expression of CREB/inducible cAMP early repressor, suggesting that this alteration is not secondary to an upstream disregulation at the receptor level. In conclusion, our results suggest that an alteration in cAMP signaling may be associated with malignancies of the adrenal cortex.

scholarly journals Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element

2003 ◽  
Vol 371 (3) ◽  
pp. 887-895 ◽  
Author(s):  
Elisabeth BALOGUN ◽  
Martha HOQUE ◽  
Pengfei GONG ◽  
Erin KILLEEN ◽  
Colin J. GREEN ◽  
...  
Keyword(s):  
Natural Antioxidants ◽  
Caffeic Acid Phenethyl Ester ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Oxygenase Activity ◽  
Mitogen Activated Protein ◽  
Haem Oxygenase ◽  
Inducible Protein ◽  
Responsive Element ◽  
Antioxidant Responsive Element

The transcription factor Nrf2, which normally exists in an inactive state as a consequence of binding to a cytoskeleton-associated protein Keap1, can be activated by redox-dependent stimuli. Alteration of the Nrf2–Keap1 interaction enables Nrf2 to translocate to the nucleus, bind to the antioxidant-responsive element (ARE) and initiate the transcription of genes coding for detoxifying enzymes and cytoprotective proteins. This response is also triggered by a class of electrophilic compounds including polyphenols and plant-derived constituents. Recently, the natural antioxidants curcumin and caffeic acid phenethyl ester (CAPE) have been identified as potent inducers of haem oxygenase-1 (HO-1), a redox-sensitive inducible protein that provides protection against various forms of stress. Here, we show that in renal epithelial cells both curcumin and CAPE stimulate the expression of Nrf2 in a concentration- and time-dependent manner. This effect was associated with a significant increase in HO-1 protein expression and haem oxygenase activity. From several lines of investigation we also report that curcumin (and, by inference, CAPE) stimulates ho-1 gene activity by promoting inactivation of the Nrf2–Keap1 complex, leading to increased Nrf2 binding to the resident ho-1 AREs. Moreover, using antibodies and specific inhibitors of the mitogen-activated protein kinase (MAPK) pathways, we provide data implicating p38 MAPK in curcumin-mediated ho-1 induction. Taken together, these results demonstrate that induction of HO-1 by curcumin and CAPE requires the activation of the Nrf2/ARE pathway.

Sign in / Sign up

Export Citation Format

Share Document