A MGF/STAT5 binding site is necessary in the distal enhancer for high prolactin induction of transfected rabbit α<i>s</i>1‐<i>casein</i>‐CAT gene transcription

Jolivet, Geneviève; L'Hotte, Corinne; Pierre, Sandra; N, Tourkine; Houdebiné, Louis‐Marie

doi:10.1016/0014-5793(96)00598-4

Cited by 23 publications

(11 citation statements)

References 28 publications

(47 reference statements)

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“…RE-1 of the 5Ј distal region is identical in its core Stat5 binding sequence to a site in the proximal HNF-6 promoter that is responsible for gene activation by GH (35), whereas RE-2 matches both a site in the prolactin-induced ␣s1 casein promoter (36) and GHRE-2 of HS7 (16). Along with results of gel-mobility shift experiments presented in Figs.…”

Section: Discussionsupporting

confidence: 67%

Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription

Chia

Ono

Woelfle

et al. 2006

Journal of Biological Chemistry

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A key agent in the anabolic actions of growth hormone (GH) is insulin-like growth factor-I (IGF-I), a 70-amino acid secreted protein with direct effects on somatic growth and tissue maintenance and repair. GH rapidly and potently stimulates IGF-I gene transcription by mechanisms independent of new protein synthesis, and recent studies have linked the transcription factor Stat5b to a regulatory network connecting the activated GH receptor on the cell membrane to the IGF-I gene in the nucleus. Here we analyze two distinct conserved GH response elements in the rat IGF-I locus that contain paired Stat5b sites. Each response element binds Stat5b in vivo in a GH-dependent way, as assessed by chromatin immunoprecipitation assays, and consists of one high affinity and one lower affinity Stat5b site, as determined by both qualitative and quantitative protein-DNA binding studies. In biochemical reconstitution experiments, both response elements are able to mediate GH-stimulated and Stat5b-dependent transcription when fused to a reporter gene containing either the major IGF-I promoter or a minimal neutral promoter, although the paired Stat5b sites located in the second IGF-I intron were more than twice as effective as the response element that mapped ϳ73 kb 5 to the IGF-I exon 1. Taken together, our results define the initial molecular architecture of a complicated GH-regulated transcriptional pathway, and suggest that apparently redundant hormone response elements provide a mechanism for amplifying GH action at a physiologically important target gene.

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Section: Discussionsupporting

confidence: 67%

Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription

Chia

Ono

Woelfle

et al. 2006

Journal of Biological Chemistry

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“…19 In addition, transgenic mice overexpressing the rat PRL gene develop dramatic enlargements of the prostate gland. The proliferation and secretory activities of prostate epithelial Evidence of a novel biomarker, as1-Casein K Xu et al cells are stimulated by PRL in rodents and men.…”

Section: Discussionmentioning

confidence: 99%

“…21 As the expression of as1-Casein is regulated by PRL in different animal models. 19,[22][23][24] It is possible that as1-Casein may act as a downstream factor of PRL which plays a key role in the development of BPH.…”

Section: Discussionmentioning

confidence: 99%

Evidence of a novel biomarker, αs1-Casein, a milk protein, in benign prostate hyperplasia

Wang

et al. 2006

Prostate Cancer Prostatic Dis

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Benign prostate hyperplasia (BPH) is a common disease in elderly men. Although it is a nonmalignant disease, it has a significant detrimental impact on the quality of life in patients with latestage disease. Owing to the lack of specific markers, diagnosis of early-stage BPH has been proven unsuccessful. Recently, using two-dimensional electrophoresis, we identified a group of prostatic secretory proteins that are specifically produced by BPH cells (Xu et al., Electrophoresis 2003; 24: 1311). In this study, we investigated the potential diagnostic value of one of the secretory proteins, as1-Casein, in BPH by inmmunohistological staining of normal, BPH and prostate cancer tissues. We found that 90% (20 out of 22) of BPH tissues showed moderate to strong as1-Casein protein expression whereas none of the normal tissues (0 out of 10) and less than 10% of the prostate cancer tissues (3 out of 30) showed similar staining intensity. Our results suggest that as1-Casein may be a potential biomarker for early identification of BPH patients.

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Section: Study Of Transcription Factorsmentioning

confidence: 99%

“…The STAT5 binding site was present in the rabbit promoter and in a distal region containing the milk box. These data were obtained using in vitro mutations, gene transfection into primary rabbit mammary cells (Devinoy et al, 1991) and gel retardation (Pierre et al, 1992 and1994;Jolivet et al, 1996).A study carried out in mice indicated that the activation of STAT5 by prolactin in cultured mammary cells occurred only in the presence of the extracellular matrix. It was concluded that the matrix inhibits a tyrosine phosphatase that deactivates STAT5 in the absence of matrix (Edwards et al, 1998).…”

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confidence: 99%

Rabbit milk protein genes: from mRNA identification to chromatin structure

Jolivet

Daniel-Carlier

Thépot

et al. 2008

Animal

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Milk protein genes are among the most intensively expressed and they are active only in epithelial mammary cells of lactating animals. They code for proteins which represent 30% of the proteins consumed by humans in developed countries. Mammary gland development occurs essentially during each pregnancy. This offers experimenters attractive models to study the expression mechanisms of genes controlled by known hormones and factors (prolactin, glucocorticoids, progesterone, insulin-like growth factor-1 and others) as well as extracellular matrix. In the mid-1970s, it became possible to identify and quantify mRNAs from higher living organisms using translation in reticulocyte lysate. A few years later, the use of radioactive cDNAs as probes made it possible for the quantification of mRNA in various physiological situations using hybridisation in the liquid phase. Gene cloning offered additional tools to measure milk protein mRNAs and also to identify transcription factors. Gene transfer in cultured mammary cells and in animals contributed greatly to these studies. It is now well established that most if not all genes of higher eukaryotes are under the control of multiple distal regulatory elements and that local modifications of the chromatin structure play an essential role in the mechanisms of differentiation from embryos to adults. The technique, known as ChIP (chromatin immunoprecipitation), is being implemented to identify the factors that modify chromatin structure at the milk protein gene level during embryo development, mammogenesis and lactogenesis, including the action of hormones and extracellular matrix. Transgenesis is not just a tool to study gene regulation and function, it is also currently used for various biotechnological applications including the preparation of pharmaceutical proteins in milk. This implies the design of efficient vectors capable of directing the secretion of recombinant proteins in milk at a high concentration. Milk protein gene promoters and long genomic-DNA fragments containing essentially all the regulatory elements of milk protein genes are used to optimise recombinant protein production in milk.Keywords: chromatin, development, promoter, transgenesis IntroductionMilk protein genes are abundantly and specifically expressed in the mammary gland of lactating mammals. Lactation is essential for the development of newborns. Since the domestication of a few ruminants, milk has become an important food for humans. Milk proteins represent 30% of the proteins consumed by humans in developed countries. On the other hand, milk protein genes are among the most intensively expressed genes and they were soon candidates to study the mechanisms of gene expression. For these reasons, biology of lactation has been extensively studied for the last 50 years. The main factors controlling mammary gland development and milk protein gene expression are well known. These factors are oestrogens, prolactin, progesterone, glucocorticoids, insulin-like growth factor-1, placental lactogen and extracellu...

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A MGF/STAT5 binding site is necessary in the distal enhancer for high prolactin induction of transfected rabbit αs1‐casein‐CAT gene transcription

Cited by 23 publications

References 28 publications

Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription

Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription

Evidence of a novel biomarker, αs1-Casein, a milk protein, in benign prostate hyperplasia

Rabbit milk protein genes: from mRNA identification to chromatin structure

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