In situ quantification of individual mRNA transcripts in melanocytes discloses gene regulation of relevance to speciation

AbstractFunctional validation of candidate genes for adaptation and speciation remains challenging. We here exemplify the utility of a method quantifying individual mRNA transcripts in revealing the molecular basis of divergence in feather pigment synthesis during early-stage speciation in crows. Using a padlock probe assay combined with rolling circle amplification we quantified cell-type specific gene expression in the native, histological context of growing feather follicles. Expression of Tyrosinase related protein 1 (TYRP1), Solute carrier family 45 member 2 (SLC45A2) and Hematopoietic prostaglandin D synthase (HPGDS) was melanocyte-limited and significantly reduced in follicles from hooded crow explaining the substantially lower melanin content in grey vs. black feathers. The central upstream transcription factor Microphthalmia-associated transcription factor (MITF) only showed differential expression specific to melanocytes - a feature not captured by bulk RNA-seq. Overall, this study provides insight into the molecular basis of an evolutionary young transition in pigment synthesis, and demonstrates the power of histologically explicit, statistically substantiated single-cell gene expression quantification for functional genetic inference in natural populations.

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Molecular basis of tissue-specific gene expression mediated by the Runt domain transcription factor PEBP2/CBF

Genes to Cells ◽

10.1046/j.1365-2443.1999.00298.x ◽

1999 ◽

Vol 4 (12) ◽

pp. 685-696 ◽

Cited By ~ 130

Author(s):

Yoshiaki Ito

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Molecular Basis ◽

Specific Gene ◽

Runt Domain ◽

Tissue Specific ◽

Tissue Specific Gene ◽

Specific Gene Expression

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Using Serial Analysis of Gene Expression to Identify Tumor Markers and Antigens

Disease Markers ◽

10.1155/2001/185929 ◽

2001 ◽

Vol 17 (2) ◽

pp. 41-48 ◽

Cited By ~ 16

Author(s):

Gregory J. Riggins

Keyword(s):

Gene Expression ◽

Tumor Markers ◽

Normal Tissue ◽

Specific Gene ◽

Cancer Genome Anatomy Project ◽

Malignant Tissue ◽

Normal Tissues ◽

Mrna Transcripts ◽

Source Of Information ◽

Sage Data

Tumor markers and antigens are normally highly expressed in malignant tissue, but not in the surrounding normal tissue. Serial Analysis of Gene Expression (SAGE) is a technology that counts mRNA transcripts and can be used to find those genes most highly induced in malignant tissues. SAGE produces a comprehensive profile of gene expression and can be used to search for tumor biomarkers in a limited number of samples. Public sources of SAGE data, in particular through the Cancer Genome Anatomy Project, increase the value of this technology by making a large source of information on many tumors and normal tissues available for comparison. Although the perfect tumor-specific gene does not exist, the differences in gene expression between tumor and normal can be exploited for therapeutic or diagnostic purposes.

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FOXA1 in breast cancer

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399409001008 ◽

2009 ◽

Vol 11 ◽

Cited By ~ 39

Author(s):

Harikrishna Nakshatri ◽

Sunil Badve

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Transcription Factor ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Gene Expression Signature ◽

Specific Gene ◽

Breast Cancers ◽

Transcription Factor Network ◽

Histopathological Classification

Breast cancer is a heterogeneous disease and classification is important for clinical management. At least five subtypes can be identified based on unique gene expression patterns; this subtype classification is distinct from the histopathological classification. The transcription factor network(s) required for the specific gene expression signature in each of these subtypes is currently being elucidated. The transcription factor network composed of the oestrogen (estrogen) receptor α (ERα), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers. Breast cancers that are dependent on this network correspond to well-differentiated and hormone-therapy-responsive tumours with good prognosis. In this review, we discuss the interplay between these transcription factors with a particular emphasis on FOXA1 structure and function, and its ability to control ERα function. Additionally, we discuss modulators of FOXA1 function, ERα–FOXA1–GATA3 downstream targets, and potential therapeutic agents that may increase differentiation through FOXA1.

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Identification of Gene Expression Signature in Estrogen Receptor Positive Breast Carcinoma

Biomarkers in Cancer ◽

10.4137/bic.s3793 ◽

2010 ◽

Vol 2 ◽

pp. BIC.S3793 ◽

Cited By ~ 23

Author(s):

Arvind D. Thakkar ◽

Hemanth Raj ◽

Debarshi Chakrabarti ◽

Ravishankar ◽

N. Saravanan ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Estrogen Receptor ◽

Transcription Factor ◽

Molecular Basis ◽

Clinical Specimen ◽

Gene Expression Signature ◽

Breast Tumors ◽

Significant Group ◽

Six Genes

A significant group of patient with estrogen receptor (ER) α positive breast tumors fails to appreciably respond to endocrine therapy. An increased understanding of the molecular basis of estrogen-mediated signal transduction and resultant gene expression may lead to novel strategies for treating breast cancer. In this study, we sought to identify the dysregulated genes in breast tumors related to ERα status. Microarray analyses of 31 tumor samples showed 108 genes differentially expressed in ERα (+) and ERα (–) primary breast tumors. Further analyses of gene lists indicated that a significant number of dysregulated genes were involved in mRNA transcription and cellular differentiation. The majority of these genes were found to have promoter-binding sites for E74-like factor 5 (ELF5; 54.6% genes), E2F transcription factor 1 (E2F1; 22.2% genes), and nuclear transcription factor Y alpha (NFYA; 32.4% genes). Six candidate genes ( NTN4, SLC7A8, MLPH, ENPP1, LAMB2, and PLAT) with differential expression were selected for further validation studies using RT-qPCR (76 clinical specimen) and immunohistochemistry (48 clinical specimen). Our studies indicate significant overexpression of all the six genes in ERα (+) breast tumors as compared to ERα (–) breast tumors. In vitro studies using T-47D breast cancer cell line confirmed the estrogen dependant expression of four of the above six genes ( SLC7A8, ENPP1, LAMB2, and PLAT). Collectively, our study provides further insights into the molecular basis of estrogen-dependent breast cancer and identifies “candidate biomarkers” that could be useful for predicting endocrine responsiveness.

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Disappearance of the sigma E transcription factor from the forespore and the SpoIIE phosphatase from the mother cell contributes to establishment of cell-specific gene expression during sporulation in Bacillus subtilis.

Journal of Bacteriology ◽

10.1128/jb.179.10.3331-3341.1997 ◽

1997 ◽

Vol 179 (10) ◽

pp. 3331-3341 ◽

Cited By ~ 77

Author(s):

K Pogliano ◽

A E Hofmeister ◽

R Losick

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Bacillus Subtilis ◽

Mother Cell ◽

Specific Gene ◽

Specific Gene Expression ◽

Sigma E

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The TEA Transcription Factor Tec1 Confers Promoter-Specific Gene Regulation by Ste12-Dependent and -Independent Mechanisms

Eukaryotic Cell ◽

10.1128/ec.00251-09 ◽

2010 ◽

Vol 9 (4) ◽

pp. 514-531 ◽

Cited By ~ 20

Author(s):

Barbara Heise ◽

Julia van der Felden ◽

Sandra Kern ◽

Mario Malcher ◽

Stefan Brückner ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcriptional Activation ◽

Binding Sites ◽

Target Genes ◽

Specific Gene ◽

Dependent Manner ◽

A Genome ◽

Regulated Gene Expression

ABSTRACT In Saccharomyces cerevisiae, the TEA transcription factor Tec1 is known to regulate target genes together with a second transcription factor, Ste12. Tec1-Ste12 complexes can activate transcription through Tec1 binding sites (TCSs), which can be further combined with Ste12 binding sites (PREs) for cooperative DNA binding. However, previous studies have hinted that Tec1 might regulate transcription also without Ste12. Here, we show that in vivo, physiological amounts of Tec1 are sufficient to stimulate TCS-mediated gene expression and transcription of the FLO11 gene in the absence of Ste12. In vitro, Tec1 is able to bind TCS elements with high affinity and specificity without Ste12. Furthermore, Tec1 contains a C-terminal transcriptional activation domain that confers Ste12-independent activation of TCS-regulated gene expression. On a genome-wide scale, we identified 302 Tec1 target genes that constitute two distinct classes. A first class of 254 genes is regulated by Tec1 in a Ste12-dependent manner and is enriched for genes that are bound by Tec1 and Ste12 in vivo. In contrast, a second class of 48 genes can be regulated by Tec1 independently of Ste12 and is enriched for genes that are bound by the stress transcription factors Yap6, Nrg1, Cin5, Skn7, Hsf1, and Msn4. Finally, we find that combinatorial control by Tec1-Ste12 complexes stabilizes Tec1 against degradation. Our study suggests that Tec1 is able to regulate TCS-mediated gene expression by Ste12-dependent and Ste12-independent mechanisms that enable promoter-specific transcriptional control.

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The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes

Molecular and Cellular Biology ◽

10.1128/mcb.00269-07 ◽

2007 ◽

Vol 27 (11) ◽

pp. 4082-4092 ◽

Cited By ~ 40

Author(s):

Andrew J. Bingham ◽

Lezanne Ooi ◽

Lukasz Kozera ◽

Edward White ◽

Ian C. Wood

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Cardiac Hypertrophy ◽

Gene Expression Profile ◽

Expression Profile ◽

Molecular Mechanisms ◽

Ventricular Myocytes ◽

Specific Gene ◽

Histone H4 Acetylation ◽

Repressor Element

ABSTRACT Cardiac hypertrophy is associated with a dramatic change in the gene expression profile of cardiac myocytes. Many genes important during development of the fetal heart but repressed in the adult tissue are reexpressed, resulting in gross physiological changes that lead to arrhythmias, cardiac failure, and sudden death. One transcription factor thought to be important in repressing the expression of fetal genes in the adult heart is the transcriptional repressor REST (repressor element 1-silencing transcription factor). Although REST has been shown to repress several fetal cardiac genes and inhibition of REST function is sufficient to induce cardiac hypertrophy, the molecular mechanisms employed in this repression are not known. Here we show that continued REST expression prevents increases in the levels of the BNP (Nppb) and ANP (Nppa) genes, encoding brain and atrial natriuretic peptides, in adult rat ventricular myocytes in response to endothelin-1 and that inhibition of REST results in increased expression of these genes in H9c2 cells. Increased expression of Nppb and Nppa correlates with increased histone H4 acetylation and histone H3 lysine 4 methylation of promoter-proximal regions of these genes. Furthermore, using deletions of individual REST repression domains, we show that the combined activities of two domains of REST are required to efficiently repress transcription of the Nppb gene; however, a single repression domain is sufficient to repress the Nppa gene. These data provide some of the first insights into the molecular mechanism that may be important for the changes in gene expression profile seen in cardiac hypertrophy.

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