Glucocorticoid Receptor-Dependent Gene Regulatory Networks

Le, Panin; Friedman, Joshua R.; Schug, Jonathan; Brestelli, John; Parker, J. Brandon; Bochkis, Irina M.; Kaestner, Klaus H.

doi:10.1371/journal.pgen.0010016

Cited by 199 publications

(108 citation statements)

References 75 publications

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“…In general, we were struck by the remarkable degree of cell and gene specificity inherent in androgen regulation, as 182 (89%) of the 205 ARGs we identified were apparently androgen-unresponsive in LNCaP cells (DePrimo et al 2002;Nelson et al 2002). Similarly, comparisons of glucocorticoid-responsive genes in different cell types (Rogatsky et al 2003;Wang et al 2004;Phuc Le et al 2005;So et al 2007) revealed little overlap. It will be important in future work to assemble expression and response data from multiple androgen-responsive cell types to better define and understand tissue-specific transcriptional networks radiating outward from AR.…”

Section: Figure 6 Distribution Analysis Of Ares Located Near Args (A)mentioning

confidence: 94%

“…Rather than focusing primarily on promoter proximal regions (Phuc Le et al 2005) or CpG islands (Weinmann et al 2002) or individual chromosomes , we developed tiled-oligonucleotide microarrays spanning ∼104 kb centered on the predicted transcription start site of each of several hundred candidate hormone-responsive genes. We assessed the relationship between receptor occupancy and hormone responsive expression, characterized the genomic organization of AR-regulated genes and AREs, surveyed the complexity and composition of the AREs, and examined the physiologic roles of the primary ARGs.…”

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confidence: 99%

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Cell- and gene-specific regulation of primary target genes by the androgen receptor

Bolton¹,

So²,

Chaivorapol³

et al. 2007

Genes Dev.

312

273

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The androgen receptor (AR) mediates the physiologic and pathophysiologic effects of androgens including sexual differentiation, prostate development, and cancer progression by binding to genomic androgen response elements (AREs), which influence transcription of AR target genes. The composition and context of AREs differ between genes, thus enabling AR to confer multiple regulatory functions within a single nucleus. We used expression profiling of an immortalized human prostate epithelial cell line to identify 205 androgen-responsive genes (ARGs), most of them novel. In addition, we performed chromatin immunoprecipitation to identify 524 AR binding regions and validated in reporter assays the ARE activities of several such regions. Interestingly, 67% of our AREs resided within ∼50 kb of the transcription start sites of 84% of our ARGs. Indeed, most ARGs were associated with two or more AREs, and ARGs were sometimes themselves linked in gene clusters containing up to 13 AREs and 12 ARGs. AREs appeared typically to be composite elements, containing AR binding sequences adjacent to binding motifs for other transcriptional regulators. Functionally, ARGs were commonly involved in prostate cell proliferation, communication, differentiation, and possibly cancer progression. Our results provide new insights into cell-and gene-specific mechanisms of transcriptional regulation of androgen-responsive gene networks.[Keywords: Androgen receptor (AR); androgen response element (ARE); transcription; steroid receptor; chromatin immunoprecipitation (ChIP); prostate cancer] Supplemental material is available at http://www.genesdev.org.

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Section: Figure 6 Distribution Analysis Of Ares Located Near Args (A)mentioning

confidence: 94%

mentioning

confidence: 99%

Cell- and gene-specific regulation of primary target genes by the androgen receptor

Bolton¹,

So²,

Chaivorapol³

et al. 2007

Genes Dev.

312

273

View full text Add to dashboard Cite

show abstract

“…Immunoprecipitated DNA was amplified to linear phase by ligation-mediated PCR as described (20). Amplified DNA was labeled using Genisphere's DNA900 labeling system (Genisphere, Hatfield, Pennsylvania) and hybridized as described fully in Supplement 1.…”

Section: Amplification Of Chip Dna and Microarray Analysismentioning

confidence: 99%

CREB Binding and Activity in Brain: Regional Specificity and Induction by Electroconvulsive Seizure

Tanis

Duman

Newton

2008

Biological Psychiatry

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Background-The transcription factor cyclic adenosine monophosphate response element binding protein (CREB) orchestrates diverse neurobiological processes including cell differentiation, survival, and plasticity. Alterations in CREB-mediated transcription have been implicated in numerous central nervous system (CNS) disorders including depression, anxiety,addiction,and cognitive decline. However, it remains unclear how CREB contributes to normal and aberrant CNS function, as the identity of CREB-regulated genes in brain and the regional and temporal dynamics of CREB function remain largely undetermined.

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“…The current study is the first to demonstrate that uterine MCs are immunopositive for nuclear GR. A glucocorticoid rich environment would favour activation of GR, with shuttling of ligand activated receptor from the cytoplasm towards the nucleus ( Phuc Le et al ., 2005). This observation would be consistent with expression 11-β hydroxysteroid dehydrogenase enzymes within the uterus, resulting in a cortisol rich microenvironment ( Gibson et al ., 2013; McDonald et al , 2006).…”

Section: Discussionmentioning

confidence: 99%

Immunoprofiling of human uterine mast cells identifies three phenotypes and expression of ERβ and glucocorticoid receptor

et al. 2017

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Background: Human mast cells (MCs) are long-lived tissue-resident immune cells characterised by granules containing the proteases chymase and/or tryptase. Their phenotype is modulated by their tissue microenvironment. The human uterus has an outer muscular layer (the myometrium) surrounding the endometrium, both of which play an important role in supporting a pregnancy. The endometrium is a sex steroid target tissue consisting of epithelial cells (luminal, glandular) surrounded by a multicellular stroma, with the latter containing an extensive vascular compartment as well as fluctuating populations of immune cells that play an important role in regulating tissue function. The role of MCs in the human uterus is poorly understood with little known about their regulation or the impact of steroids on their differentiation status. The current study had two aims: 1) To investigate the spatial and temporal location of uterine MCs and determine their phenotype; 2) To determine whether MCs express receptors for steroids implicated in uterine function, including oestrogen (ERα, ERβ), progesterone (PR) and glucocorticoids (GR). Methods: Tissue samples from women (n=46) were used for RNA extraction or fixed for immunohistochemistry. Results: Messenger RNAs encoded by TPSAB1 (tryptase) and CMA1 (chymase) were detected in endometrial tissue homogenates. Immunohistochemistry revealed the relative abundance of tryptase MCs was myometrium>basal endometrium>functional endometrium. We show for the first time that uterine MCs are predominantly of the classical MC subtypes: (positive, +; negative, -) tryptase+/chymase- and tryptase+/chymase+, but a third subtype was also identified (tryptase-/chymase+). Tryptase+ MCs were of an ERβ+/ERα-/PR-/GR+ phenotype mirroring other uterine immune cell populations, including natural killer cells. Conclusions: Endometrial tissue resident immune MCs have three protease-specific phenotypes. Expression of both ERβ and GR in MCs mirrors that of other immune cells in the endometrium and suggests that MC function may be altered by the local steroid microenvironment.

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Glucocorticoid Receptor-Dependent Gene Regulatory Networks

Cited by 199 publications

References 75 publications

Cell- and gene-specific regulation of primary target genes by the androgen receptor

Cell- and gene-specific regulation of primary target genes by the androgen receptor

CREB Binding and Activity in Brain: Regional Specificity and Induction by Electroconvulsive Seizure

Immunoprofiling of human uterine mast cells identifies three phenotypes and expression of ERβ and glucocorticoid receptor

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