In Vivo Tissue-Specific Regulation of the Human Papillomavirus Type 18 Early Promoter by Estrogen, Progesterone, and Their Antagonists

ABSTRACT The Ets family transcription factor PU.1 is crucial for the regulation of hematopoietic development. Pu.1 is activated in hematopoietic stem cells and is expressed in mast cells, B cells, granulocytes, and macrophages but is switched off in T cells. Many of the transcription factors regulating Pu.1 have been identified, but little is known about how they organize Pu.1 chromatin in development. We analyzed the Pu.1 promoter and the upstream regulatory element (URE) using in vivo footprinting and chromatin immunoprecipitation assays. In B cells, Pu.1 was bound by a set of transcription factors different from that in myeloid cells and adopted alternative chromatin architectures. In T cells, Pu.1 chromatin at the URE was open and the same transcription factor binding sites were occupied as in B cells. The transcription factor RUNX1 was bound to the URE in precursor cells, but binding was down-regulated in maturing cells. In PU.1 knockout precursor cells, the Ets factor Fli-1 compensated for the lack of PU.1, and both proteins could occupy a subset of Pu.1 cis elements in PU.1-expressing cells. In addition, we identified novel URE-derived noncoding transcripts subject to tissue-specific regulation. Our results provide important insights into how overlapping, but different, sets of transcription factors program tissue-specific chromatin structures in the hematopoietic system.

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Tissue-specific regulation of sialyltransferase activities in the rat by corticosteroids in vivo

Glycobiology ◽

10.1093/glycob/6.1.15 ◽

1996 ◽

Vol 6 (1) ◽

pp. 15-22 ◽

Cited By ~ 29

Author(s):

Christine M. Coughlan ◽

Jonathan R. Seckl ◽

David J. Fox ◽

Robin Unsworth ◽

Kieran C. Breen

Keyword(s):

Tissue Specific ◽

Specific Regulation

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Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function

Blood ◽

10.1182/blood.v97.7.2091 ◽

2001 ◽

Vol 97 (7) ◽

pp. 2091-2097 ◽

Cited By ~ 33

Author(s):

Carsten Müller-Tidow ◽

Wenbing Wang ◽

Gregory E. Idos ◽

Sven Diederichs ◽

Rong Yang ◽

...

Keyword(s):

Leukemic Cells ◽

Glutathione S Transferase ◽

Cyclin A1 ◽

Tissue Specific ◽

Cdk2 Complex ◽

Cyclin A2 ◽

Specific Regulation ◽

Phosphopeptide Mapping

Abstract Cyclin A1 is tissue-specifically expressed during spermatogenesis, but it is also highly expressed in acute myeloid leukemia (AML). Its pathogenetic role in AML and in the cell cycle of leukemic blasts is unknown. B-myb is essential for G1/S transition and has been shown to be phosphorylated by the cyclin A2/cdk2 complex. Here it is demonstrated that cyclin A1 interacts with the C-terminal portion of B-myb as shown by glutathione S-transferase (GST) precipitation. This interaction is confined to cyclin A1 because binding could not be detected between cyclin A2 and B-myb. Also, cdk2 was not pulled down by GST–B-myb from U937 lysates. In addition, co-immunoprecipitation of cyclin A1 and B-myb in leukemic cells evidenced protein interaction in vivo. Baculovirus-expressed cyclin A1/cdk2 complexes were able to phosphorylate human as well as murine B-myb in vitro. Tryptic phosphopeptide mapping revealed that cyclin A1/cdk2 complexes phosphorylated the C-terminal part of B-myb at several sites including threonine 447, 490, and 497 and serine 581. These phosphorylation sites have been demonstrated to be important for the enhancement of B-myb transcriptional activity. Further studies showed that cyclin A1 cooperated with B-myb to transactivate myb binding site containing promoters including the promoter of the human cyclin A1 gene. Taken together, the data suggest that cyclin A1 is a tissue-specific regulator of B-myb function and activates B-myb in leukemic blasts.

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TISSUE-SPECIFIC REGULATION OF INSULIN-LIKE GROWTH FACTORS AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS IN MALE DIABETIC RATS IN VIVO AND IN VITRO

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.2006.04495.x ◽

2006 ◽

Vol 33 (12) ◽

pp. 1172-1179 ◽

Cited By ~ 12

Author(s):

Ho Jae Han ◽

Chang Won Kang ◽

Soo Hyun Park

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Binding Proteins ◽

Diabetic Rats ◽

Tissue Specific ◽

Factor Binding ◽

Specific Regulation ◽

Insulin Like Growth Factors

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Homeoproteins CDP and SATB1 Interact: Potential for Tissue-Specific Regulation

Molecular and Cellular Biology ◽

10.1128/mcb.19.7.4918 ◽

1999 ◽

Vol 19 (7) ◽

pp. 4918-4926 ◽

Cited By ~ 37

Author(s):

Jinqi Liu ◽

Anna Barnett ◽

Ellis J. Neufeld ◽

Jaquelin P. Dudley

Keyword(s):

T Cells ◽

Dna Binding ◽

Promoter Region ◽

Cell Type ◽

Tissue Specific ◽

Specific Antisera ◽

Mmtv Promoter ◽

Specific Regulation

ABSTRACT Homeoproteins are known to participate in development and cell type specification. The homeoproteins CCAAT displacement protein (CDP) and special AT-rich sequence binding protein 1 (SATB1) have been shown to bind to nuclear matrix-associated regions and to act as repressors of many cellular genes. Moreover, binding of SATB1 to the mouse mammary tumor virus (MMTV) promoter region dramatically affects the tissue-specific transcription of this retrovirus. Because protein-protein interactions are a common means of regulating homeoprotein function, we tested whether SATB1 and CDP interact in vivo and in vitro. SATB1 interacted with CDP through its DNA-binding domain, as demonstrated by glutathione S-transferase (GST) pull-down assays. GST pull-down assays also showed that CDP associated with SATB1 through three of its four DNA-binding domains (CR1, CR2, and the homeodomain). SATB1-specific antisera, but not preimmune sera, precipitated CDP from nuclear extracts, and CDP-specific antisera precipitated SATB1 from the same extracts. Far-Western blotting detected interaction of SATB1 and CDP in several different tissue extracts. Association of purified SATB1 and CDP in vitro resulted in the inability of each protein to bind to DNA in gel retardation assays. CDP overexpression in cultured T cells led to a loss of detectable SATB1 binding to the MMTV promoter region, as measured by gel shift experiments. CDP overexpression also elevated MMTV long terminal repeat reporter gene activity in transient-transfection assays, a result consistent with neutralization of the SATB1 repressor function in T cells. SATB1 is very abundant in certain tissues, particularly thymus, whereas CDP is relatively ubiquitous, except in certain terminally differentiated cell types. Because of the tissue and cell type distribution of SATB1 and CDP, we propose that the SATB1-to-CDP ratio in different tissues is a novel mechanism for homeoproteins to control gene expression and differentiation in mammals.

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Tissue-specific regulation of medium-chain acyl-CoA dehydrogenase gene by thyroid hormones in the developing rat

Biochemical Journal ◽

10.1042/bj3240289 ◽

1997 ◽

Vol 324 (1) ◽

pp. 289-294 ◽

Cited By ~ 20

Author(s):

Fatima DJOUADI ◽

Béatrice RIVEAU ◽

Claudie MERLET-BENICHOU ◽

Jean BASTIN

Keyword(s):

Gene Expression ◽

Enzyme Activity ◽

Fatty Acid ◽

Thyroid Hormones ◽

Mrna Abundance ◽

Tissue Specific ◽

Medium Chain ◽

Chain Acyl ◽

Specific Regulation

During development, gene expression of medium-chain acyl-CoA dehydrogenase (MCAD), a nuclear-encoded mitochondrial enzyme that catalyses the first step of medium-chain fatty acid β-oxidation, is highly regulated in tissues in accordance with fatty acid utilization, but the factors involved in this regulation are largely unknown. To investigate a possible role of thyroid hormones, rat pups were made hypothyroid by the administration of propylthiouracyl to the mother from day 12 of gestation, and their kidneys, heart and liver were removed on postnatal day 16 to determine MCAD mRNA abundance, protein level and enzyme activity. Similar experiments were run in 3,3′,5-tri-iodothyronine (T3)-replaced hypothyroid (1 μg of T3/100 g body weight from postnatal day 5 to 15) and euthyroid pups. Hypothyroidism led to an increase in MCAD mRNA abundance in kidney and a decrease in abundance in heart, but had no effect in liver. The protein levels and enzyme activity were lowered in hypothyroid heart and kidney, suggesting that hypothyroidism affects post-transcriptional steps of gene expression in the kidney. All the effects of hypothyroidism were completely reversed in both heart and kidney by T3 replacement. Injection of a single T3 dose into 16-day-old euthyroid rats also led to tissue-specific changes in mRNA abundance. Nuclear run-on assays performed from hypothyroid and hypothyroid plus T3 rats showed that T3 stimulates MCAD gene transcription in heart and represses it in the kidney. These results indicate that the postnatal rise in circulating T3 is essential to the developmental regulation of the MCAD gene in vivo.

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Tissue-specific gene expression of prolactin receptor in the acute-phase response induced by lipopolysaccharides

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00522.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. E750-E757 ◽

Cited By ~ 20

Author(s):

Ana M. Corbacho ◽

Giuseppe Valacchi ◽

Lukas Kubala ◽

Estibaliz Olano-Martín ◽

Bettina C. Schock ◽

...

Keyword(s):

Acute Phase ◽

Acute Phase Response ◽

Prolactin Receptor ◽

Phase Response ◽

Specific Gene ◽

Mrna Levels ◽

Tissue Specific ◽

Specific Regulation

Acute inflammation can elicit a defense reaction known as the acute-phase response (APR) that is crucial for reestablishing homeostasis in the host. The role for prolactin (PRL) as an immunomodulatory factor maintaining homeostasis under conditions of stress has been proposed; however, its function during the APR remains unclear. Previously, it was shown that proinflammatory cytokines characteristic of the APR (TNF-α, IL-1β, and IFNγ) induced the expression of the PRL receptor (PRLR) by pulmonary fibroblasts in vitro. Here, we investigated the in vivo expression of PRLR during lipopolysaccharide (LPS)-induced APR in various tissues of the mouse. We show that PRLR mRNA and protein levels were downregulated in hepatic tissues after intraperitoneal LPS injection. Downregulation of PRLR in the liver was confirmed by immunohistochemistry. A suppressive effect on mRNA expression was also observed in prostate, seminal vesicle, kidney, heart, and lung tissues. However, PRLR mRNA levels were increased in the thymus, and no changes were observed in the spleen. The proportion of transcripts for the different receptor isoforms (long, S1, S2, and S3) in liver and thymus was not altered by LPS injection. These findings suggest a complex tissue-specific regulation of PRLR expression in the context of the APR.

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In Vivo Analysis of Developmentally and Evolutionarily Dynamic Protein-DNA Interactions Regulating Transcription of the Pgk2 Gene during Mammalian Spermatogenesis

Molecular and Cellular Biology ◽

10.1128/mcb.00990-07 ◽

2007 ◽

Vol 27 (22) ◽

pp. 7871-7885 ◽

Cited By ~ 32

Author(s):

Hirotaka Yoshioka ◽

Christopher B. Geyer ◽

Jacey L. Hornecker ◽

Krishan T. Patel ◽

John R. McCarrey

Keyword(s):

Phosphoglycerate Kinase ◽

Gene Promoter ◽

Specific Protein ◽

Dna Interactions ◽

Tissue Specific ◽

Rate Limiting Step ◽

Protein Dna Interactions ◽

Genes Encoding ◽

Specific Regulation

ABSTRACT Transcription of the testis-specific Pgk2 gene is selectively activated in primary spermatocytes to provide a source of phosphoglycerate kinase that is critical to normal motility and fertility of mammalian spermatozoa. We examined dynamic changes in protein-DNA interactions at the Pgk2 gene promoter during murine spermatogenesis in vivo by performing genomic footprinting and chromatin immunoprecipitation assays with enriched populations of murine spermatogenic cells at stages prior to, during, and following transcription of this gene. We found that genes encoding the testis-specific homeodomain factor PBX4 and its coactivator, PREP1, are expressed in patterns that mirror expression of the Pgk2 gene and that these factors become bound to the Pgk2 enhancer in cells in which this gene is actively expressed. We therefore suggest that these factors, along with CREM and SP3, direct stage- and cell type-specific transcription of the Pgk2 gene during spermatogenesis. We propose that binding of PBX4, plus its coactivator PREP1, is a rate-limiting step leading to the initiation of tissue-specific transcription of the Pgk2 gene. This study provides insight into the developmentally dynamic establishment of tissue-specific protein-DNA interactions in vivo. It also allows us to speculate about the events that led to tissue-specific regulation of the Pgk2 gene during mammalian evolution.

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Tissue-specific regulation and function of Grb10 during growth and neuronal commitment

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1411254111 ◽

2014 ◽

Vol 112 (22) ◽

pp. 6841-6847 ◽

Cited By ~ 30

Author(s):

Robert N. Plasschaert ◽

Marisa S. Bartolomei

Keyword(s):

Motor Neurons ◽

Cellular Proliferation ◽

Neuronal Development ◽

Embryonic Stem ◽

Specific Expression ◽

Tissue Specific ◽

Specific Regulation ◽

And Function

Growth-factor receptor bound protein 10 (Grb10) is a signal adapter protein encoded by an imprinted gene that has roles in growth control, cellular proliferation, and insulin signaling. Additionally, Grb10 is critical for the normal behavior of the adult mouse. These functions are paralleled by Grb10’s unique tissue-specific imprinted expression; the paternal copy of Grb10 is expressed in a subset of neurons whereas the maternal copy is expressed in most other adult tissues in the mouse. The mechanism that underlies this switch between maternal and paternal expression is still unclear, as is the role for paternally expressed Grb10 in neurons. Here, we review recent work and present complementary data that contribute to the understanding of Grb10 gene regulation and function, with specific emphasis on growth and neuronal development. Additionally, we show that in vitro differentiation of mouse embryonic stem cells into alpha motor neurons recapitulates the switch from maternal to paternal expression observed during neuronal development in vivo. We postulate that this switch in allele-specific expression is related to the functional role of Grb10 in motor neurons and other neuronal tissues.

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Tissue-Specific Regulation of HNK-1 Biosynthesis by Bisecting GlcNAc

Molecules ◽

10.3390/molecules26175176 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5176

Author(s):

Haruka Kawade ◽

Jyoji Morise ◽

Sushil K. Mishra ◽

Shuta Tsujioka ◽

Shogo Oka ◽

...

Keyword(s):

Dynamics Simulation ◽

The Novel ◽

Tissue Specific ◽

Synaptic Functions ◽

The Difference ◽

Specific Regulation ◽

The Brain ◽

Bisecting Glcnac

Human natural killer—1 (HNK-1) is a sulfated glyco-epitope regulating cell adhesion and synaptic functions. HNK-1 and its non-sulfated forms, which are specifically expressed in the brain and the kidney, respectively, are distinctly biosynthesized by two homologous glycosyltransferases: GlcAT-P in the brain and GlcAT-S in the kidney. However, it is largely unclear how the activity of these isozymes is regulated in vivo. We recently found that bisecting GlcNAc, a branching sugar in N-glycan, suppresses both GlcAT-P activity and HNK-1 expression in the brain. Here, we observed that the expression of non-sulfated HNK-1 in the kidney is unexpectedly unaltered in mutant mice lacking bisecting GlcNAc. This suggests that the biosynthesis of HNK-1 in the brain and the kidney are differentially regulated by bisecting GlcNAc. Mechanistically, in vitro activity assays demonstrated that bisecting GlcNAc inhibits the activity of GlcAT-P but not that of GlcAT-S. Furthermore, molecular dynamics simulation showed that GlcAT-P binds poorly to bisected N-glycan substrates, whereas GlcAT-S binds similarly to bisected and non-bisected N-glycans. These findings revealed the difference of the highly homologous isozymes for HNK-1 synthesis, highlighting the novel mechanism of the tissue-specific regulation of HNK-1 synthesis by bisecting GlcNAc.

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