scholarly journals Higher-order chromatin organization defines Progesterone Receptor and PAX2 binding to regulate estradiol-primed endometrial cancer gene expression

2019 ◽  
Author(s):  
Alejandro La Greca ◽  
Nicolás Bellora ◽  
Francois Le Dily ◽  
Rodrigo Jara ◽  
Javier Quilez Oliete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Binding Sites ◽  
Specific Binding ◽  
Open Chromatin ◽  
Cancer Gene ◽  
Specific Binding Sites ◽  
Endometrial Tumor ◽  
Long Range Interactions ◽  
Specific Receptors

AbstractEstrogen (E2) and Progesterone (Pg), via their specific receptors (ER and PR respectively), are major determinants in the development and progression of endometrial malignancies. Here, we have studied how E2 and the synthetic progestin R5020 affect genomic functions in Ishikawa endometrial cancer cells. Using ChIPseq in cells exposed to the corresponding hormones, we identified cell specific binding sites for ER (ERbs) and PR (PRbs), which mostly correspond to independent sites but both adjacent to sites bound by PAX2. Analysis of long-range interactions by Hi-C showed enrichment of regions co-bound by PR and PAX2 inside TADs that contain differentially progestin-regulated genes. These regions, which we call “progestin control regions” (PgCRs), exhibit an open chromatin state prior to the exposure to the hormone. Our observations suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with partner transcription factors to PgCRs, compartmentalizing hormone-independent open chromatin.

scholarly journals Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Alejandro La Greca ◽  
Nicolás Bellora ◽  
François Le Dily ◽  
Rodrigo Jara ◽  
Ana Silvina Nacht ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
Target Genes ◽  
Fine Tuning ◽  
Open Chromatin ◽  
Altered Expression ◽  
Endometrial Tumor ◽  
Long Range Interactions ◽  
Specific Receptors ◽  
Endometrial Carcinomas

Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call 'progestin control regions' (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.

scholarly journals Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland

1998 ◽  
Vol 157 (1) ◽  
pp. 99-106 ◽  
Author(s):  
G Muccioli ◽  
C Ghe ◽  
MC Ghigo ◽  
M Papotti ◽  
E Arvat ◽  
...  
Keyword(s):  
Substance P ◽  
Human Brain ◽  
Pituitary Gland ◽  
Binding Sites ◽  
Specific Binding ◽  
Scatchard Analysis ◽  
Dependent Manner ◽  
Gh Secretagogues ◽  
Specific Binding Sites ◽  
Specific Receptors

In vitro studies have been performed to demonstrate and characterize specific binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary gland and different human brain regions. A binding assay for sGHS was established using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high specific activity at the Tyr residue. Specific binding sites for 125I-labelled Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland and hypothalamus, but they were also present in other brain areas such as choroid plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related differences. In contrast, negligible binding was found in the thalamus, striatum, substantia nigra, cerebellum and corpus callosum. The binding of 125I-labelled Tyr-Ala-hexarelin to membrane-binding sites is a saturable and reversible process, depending on incubation time and pH of the buffer. Scatchard analysis of the binding revealed a finite number of binding sites in the hypothalamus and pituitary gland with a dissociation constant (Kd) of (1.5 +/- 0.3) x 10(-9) and (2.1 +/- 0.4) x 10(-9) mol/l respectively. Receptor activity is sensitive to trypsin and phospholipase C digestion, suggesting that protein and phospholipids are essential for the binding of 125I-labelled Tyr-Ala-hexarelin. The binding of 125I-labelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was displaced in a dose-dependent manner by different unlabelled synthetic peptidyl (Tyr-Ala-hexarelin, GHRP2, hexarelin, GHRP6) and non-peptidyl (MK 0677) sGHS. An inhibition of the specific binding was also observed when binding was performed in the presence of [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P, a substance P antagonist that has been found to inhibit GH release in response to sGHS. In contrast, no competition was observed in the presence of other neuropeptides (GHRH, somatostatin, galanin or Met-enkephalin) which have a known influence on GH release. In conclusion, the present data demonstrate that sGHS have specific receptors in human brain and pituitary gland and reinforce the hypothesis that these compounds could be the synthetic counterpart of an endogenous GH secretagogue involved in the neuroendocrine control of GH secretion and possibly in other central activities.

Chick hepatic lectins: An electron microscopic study on isolated hepatocytes during development

1991 ◽  
Vol 11 (5) ◽  
pp. 257-264
Author(s):  
L. Falasca ◽  
P. Mattioli ◽  
L. Dini
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Ultrastructural Level ◽  
Isolated Hepatocytes ◽  
Cell Surfaces ◽  
Electron Microscopic ◽  
Specific Binding Sites ◽  
Neonatal Life ◽  
Specific Receptors ◽  
Recognition Systems

We studied the carbohydrate recognition systems of hepatocytes isolated from 16-day-old embryos, 19-day-old embryos and chicks within 24 h of hatching. We localized and quantified at the ultrastructural level the binding sites for glycoproteins exposing terminal N-acetylglucosamine (GlcNAc), mannose and N-acetylgalactosamine (GalNAc) residues by means of protein-gold complexes. Binding sites specific for GlcNAc and mannose residues are present on hepatocytes from embryos and chicks. On the contrary GalNAc specific binding sites are exclusively observed on cells from 16-day-old embryos. The number and distribution of gold particles on hepatocyte cell surfaces depend on the binding sites and the age considered. We describe a modulation in the number of GlcNAc, and mannose specific receptors present on the cell surface between the embryonal stage and neonatal life.

Identification of trophoblast-specific binding sites for GATA-2 that are essential for rat placental lactogen-I gene expression

2009 ◽  
Vol 31 (8) ◽  
pp. 1173-1181 ◽  
Author(s):  
Gon-Sup Kim ◽  
Yeoung-Gyu Ko ◽  
Oh-Sung Park ◽  
Hyoung Joon Park ◽  
Phil-Ok Koh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Specific Binding ◽  
Placental Lactogen ◽  
Specific Binding Sites ◽  
I Gene

Ontogeny of prolactin receptors in rat decidual tissue: binding by a locally produced prolactin-like hormone

1986 ◽  
Vol 110 (1) ◽  
pp. 115-121 ◽  
Author(s):  
P. G. Jayatilak ◽  
G. Gibori
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Prolactin Receptor ◽  
Prolactin Receptors ◽  
Decidual Tissue ◽  
Physiological And Biochemical Characteristics ◽  
Specific Binding Sites ◽  
Specific Receptors ◽  
Physiological And Biochemical

ABSTRACT The objectives of this investigation were to determine whether decidual tissue possesses specific binding sites for prolactin, and to examine whether the locally produced prolactin-like hormone binds to these receptors. Characterization of the binding of prolactin to decidual tissue from rats at day 9 of pseudopregnancy revealed specific, high-affinity sites. Binding approached saturation with increasing concentrations of either the ligand or the protein. Cytosolic extracts of day-9 decidual tissue, containing various amounts of decidual luteotrophin which possesses several of the physiological and biochemical characteristics of prolactin, displaced the binding of 125I-labelled prolactin to decidual membranes in a linear fashion. Prolactin-binding sites were detectable 72 h after induction of decidualization and 48 h after the appearance of decidual luteotrophin in the decidua. Prolactin receptor concentrations increased significantly between days 8 and 9, reached a plateau between days 9 and 12 and declined abruptly on days 14 and 15, accompanied by a similar decline in decidual luteotrophin concentration in the tissue. Thus rat decidual tissue possesses specific receptors for prolactin to which decidual luteotrophin locally produced can bind, thereby suggesting an auto/paracrine role for this substance. J. Endocr. (1986) 110, 115–121

scholarly journals Specific Binding of Rubidium in Chlorella

1962 ◽  
Vol 45 (5) ◽  
pp. 959-977 ◽  
Author(s):  
Dan Cohen
Keyword(s):  
Active Transport ◽  
Binding Sites ◽  
Specific Binding ◽  
High Concentration ◽  
External Concentration ◽  
Specific Binding Sites ◽  
Dense Suspension ◽  
Concentration Of Ions ◽  
The Individual ◽  
A Site

Specific binding sites for potassium, which may be components of the carriers for active transport for K in Chlorella, were characterized by their capacity to bind rubidium. A dense suspension was allowed to take up Rb86 from a low concentration of Rb86 and a high concentration of ions which saturate non-specific sites. The amount bound was derived from the increase in the external concentration of Rb86 following addition of excess potassium. The sites were heterogeneous. The average affinity of Rb and various other ions for the sites was determined by plotting the degree of displacement of Rb86 against log molar concentration of the individual ions. Interpolation gave the concentration for 50 per cent displacement of Rb, which is inversely related to affinity. The order of affinity was not changed when the cells were frozen, or boiled either in water or in 70 per cent ethanol. The affinity is maximal for ions with a crystalline radius of 1.3 to 1.5 A and a high polarizability, and is not related to the hydrated radius or valency. It is suggested that binding groups in a site are rigidly arranged, the irregular space between them being 2.6 to 3.0 A across, so that affinity is high for ions of this diameter and high polarizability.

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