TRES: comparative promoter sequence analysis

Katti, Mukund V.; Sakharkar, Meena Kishore; Ranjekar, P. K.; Gupta, Vidya S.

doi:10.1093/bioinformatics/16.8.739

Cited by 12 publications

(8 citation statements)

References 10 publications

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“…Additionally, there are no E2F sites in the PR enhancer, and PR is not known to be regulated through the cell cycle. Rather, a transcription regulatory element search (TRES) of the core region of this PR enhancer identified conserved sites for AP4, E47, Sox-5, and HOXA9 (18). Since the PR enhancer is now a well-characterized endogenous target sequence that is regulated by both increased and decreased cyclin D1 levels, identification of combinations of transcription factors involved in its regulation would be important to gain a better understanding of mechanisms explaining cyclin D1's role in gene expression control.…”

Section: Vol 30 2010 Estrogen-progesterone-cyclin D1 Effects 3123mentioning

confidence: 99%

Cyclin D1 Enhances the Response to Estrogen and Progesterone by Regulating Progesterone Receptor Expression

Yang

Chen

et al. 2010

Molecular and Cellular Biology

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Estrogen and progesterone are the defining hormones of normal female development, and both play critical roles in breast carcinogenesis. Cyclin D1 is a breast cancer oncogene whose amplification is linked to poor prognosis in estrogen and progesterone receptor-positive breast cancers. Here we report that cyclin D1 regulates progesterone receptor expression, consequently enhancing responses to estrogen and progesterone. Estrogen treatment of cyclin D1 transgenic mice increased progesterone receptor expression and induced mammary hyperplasias that were stimulated by progesterone and blocked by a progesterone antagonist. Progesterone receptor levels decreased in cyclin D1 knockout mice. Cyclin D1 regulated progesterone receptor expression through a novel estrogen-and cyclin D1-responsive enhancer in DNA encoding part of the 3 untranslated region of the progesterone receptor gene. Small inhibitory RNAs for cyclin D1 decreased progesterone receptor expression and estrogen receptor binding to the 3 enhancer region in human breast cancer cells. Since estrogen and progesterone regulate cyclin D1, our results suggest that cyclin D1's participation in a feed-forward loop could contribute to increased breast cancer risks associated with estrogen and progesterone combinations. Additionally, its regulation of the progesterone receptor identifies a novel role for cyclin D1 in ovarian hormone control of breast development and breast carcinogenesis.We have long known that ovarian hormones control normal breast development (13). Likewise, the connection between ovarian hormones and breast cancer was first therapeutically exploited over 100 years ago (3). While estrogen and progesterone (Pgr) combine to regulate normal breast development during pregnancy, the Women's Health Initiative study of hormone replacement has clearly demonstrated an increased breast cancer risk when progestins are combined with estrogen (7). This result reinvigorated the view that combinations of progesterone with estrogen can be carcinogenic.Cyclin D1 (CCND1) is a multifunctional G 1 -phase cyclin whose regulatory effects are particularly important in breast development and cancer (44). The cloning of cyclin D1 at 11q13 translocation breakpoints in parathyroid and mantle cell tumors was strong evidence of its oncogenic function, and evidence indicating that D1 was a G 1 cyclin was a key finding that linked cancer to perturbations of the cell cycle. Extensive evidence links cyclin D1 to cyclin-dependent kinase regulation of the cell cycle (27), although a recent report demonstrates that it also acts in transcriptional control (4). 11q13 amplification has been repeatedly demonstrated in breast cancers (22) where CCND1 overexpression has been linked to estrogen and progesterone receptor (PR) status. This linkage was first attributed to cyclin D1's regulation by estrogen and progesterone (12, 37). In this model, CCND1 is proposed to contribute to poor treatment response of estrogen receptor (ER)-positive tumors by acting downstream to promote hormone agonist...

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Section: Vol 30 2010 Estrogen-progesterone-cyclin D1 Effects 3123mentioning

confidence: 99%

Cyclin D1 Enhances the Response to Estrogen and Progesterone by Regulating Progesterone Receptor Expression

Yang

Chen

et al. 2010

Molecular and Cellular Biology

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“…In light of different regions of vertebrate genomes diverging at dissimilar rates (43) and this heterotachy being witnessed across different classes of mutation and lineages (44), this study utilized a variety of comparative alignment and transcription factor binding site search techniques with parameters that were appropriate for the evolutionary distances between species in order to detect meaningful evolutionary conserved regions (ECRs). The computational tools included CLUSTAL W (45), T-Coffee (46), GraphAlign (47), ECR Browser (48), Mulan (49), zPicture (50), TRES (51), and TRANSFAC (52).…”

Section: Homology Between Insulin Promotersmentioning

confidence: 99%

Comparative Analysis of Insulin Gene Promoters

2006

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DNA sequences that regulate expression of the insulin gene are located within a region spanning ϳ400 bp that flank the transcription start site. This region, the insulin promoter, contains a number of cis-acting elements that bind transcription factors, some of which are expressed only in the ␤-cell and a few other endocrine or neural cell types, while others have a widespread tissue distribution. The sequencing of the genome of a number of species has allowed us to examine the manner in which the insulin promoter has evolved over a 450 million-year period. The major findings are that the A-box sites that bind PDX-1 are among the most highly conserved regulatory sequences, and that the conservation of the C1, E1, and CRE sequences emphasize the importance of MafA, E47/␤2, and cAMP-associated regulation. The review also reveals that of all the insulin gene promoters studied, the rodent insulin promoters are considerably dissimilar to the human, leading to the conclusion that extreme care should be taken when extrapolating rodent-based data on the insulin gene to humans. Diabetes 55:3201-3213, 2006

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“…4C). Bioinformatic analysis of the conserved motif M1 using the TRES web server (TRES: comparative promoter sequence analysis; Katti et al 2000) showed that this conserved motif did not match any of the 222 TRANSFAC consensus binding site positional weight matrices or any of the 5919 experimentally characterized sites present in the TRES database. We also used the recently described software tool STAMP, which is specifically designed to predict the identity or structural class of proteins binding to a given sequence motif (Mahony et al 2007).…”

Section: Genome Research 1425mentioning

confidence: 99%

A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity

Smith

Sánchez²,

Follows³

et al. 2008

Genome Res.

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Altered cis-regulation is thought to underpin much of metazoan evolution, yet the underlying mechanisms remain largely obscure. The stem cell leukemia TAL1 (also known as SCL) transcription factor is essential for the normal development of blood stem cells and we have previously shown that the Tal1 +19 enhancer directs expression to hematopoietic stem cells, hematopoietic progenitors, and to endothelium. Here we demonstrate that an adjacent region 1 kb upstream (+18 element) is in an open chromatin configuration and carries active histone marks but does not function as an enhancer in transgenic mice. Instead, it boosts activity of the +19 enhancer both in stable transfection assays and during differentiation of embryonic stem (ES) cells carrying single-copy reporter constructs targeted to the Hprt locus. The +18 element contains a mammalian interspersed repeat (MIR) which is essential for the +18 function and which was transposed to the Tal1 locus ∼160 million years ago at the time of the mammalian/marsupial branchpoint. Our data demonstrate a previously unrecognized mechanism whereby enhancer activity is modulated by a transposon exerting a "booster" function which would go undetected by conventional transgenic approaches.

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TRES: comparative promoter sequence analysis

Cited by 12 publications

References 10 publications

Cyclin D1 Enhances the Response to Estrogen and Progesterone by Regulating Progesterone Receptor Expression

Cyclin D1 Enhances the Response to Estrogen and Progesterone by Regulating Progesterone Receptor Expression

Comparative Analysis of Insulin Gene Promoters

A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity

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