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GSE13285
Mus musculus, Homo sapiens
1 Downloadable Sample
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders.
Publication Title
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Description
The objective of this study was to understand the genetic mechanisms of Vitamin-A-Deficiency (VAD)-induced arrest of spermatogonial stem-cell differentiation. Vitamin A and its derivatives (the retinoids) participate in many physiological processes including vision, cellular differentiation and reproduction. VAD affects spermatogenesis, the subject of our present study. Spermatogenesis is a highly regulated process of differentiation and complex morphologic alterations that, in the postnatal testis, leads to the formation of sperm in the seminiferous epithelium. VAD causes early cessation of spermatogenesis, characterized by degeneration of meiotic germ cells, leading to seminiferous tubules containing mostly type A spermatogonia and Sertoli cells. In this study, we investigated the molecular basis of VAD on spermatogenesis in mice. We used adult Balb/C mice fed with a Control or VAD diet for an extended period of time (8-28 weeks) and selected two time points (18 and 25 weeks) for microarray analysis.
Publication Title
Long-term vitamin A deficiency induces alteration of adult mouse spermatogenesis and spermatogonial differentiation: direct effect on spermatogonial gene expression and indirect effects via somatic cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The present study reports an unbiased analysis of the cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified in the phosphoproteomic screen were transcription activators, co-repressors and chromatin regulators. A focus on the chromatin regulators revealed that CTLs have high expression of the histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of the CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators in CTLs and determine the CTL functional program. We used Affymetrix microarray analysis to explore the molecular basis for the role of HDAC7 in CTLs and the impact of GFP-HDAC7 phosphorylation deficient mutant expression on the CTL transcriptional profile.
Publication Title
Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
On triggering of the T cell receptor CD8 T lymphocytes downregulate expression of the transcription factor KLF2. KLF2 expression remains low as these cells differentiate to Cytotoxic T lymphocytes (CTL) but may be re-expressed depending on the local environmental signals.
Publication Title
The impact of KLF2 modulation on the transcriptional program and function of CD8 T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
The mechanisms involved in epithelium-stroma interactions remain poorly understood, despite the importance of the microenvironment during tumorigenesis. Here, we studied the role of Ets2 transcrpiton factor in tumor associated fibroblasts in the MMTV-ErbB2 mammary tumor model. Inactivation of Ets2 specifically in fibroblasts using Fsp-cre significantly reduced tumor growth, in contrast to Ets2 inactivation in epithelium in which no differences in tumor growth were observed.
Publication Title
Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
Description
SV40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg and TAg-mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used enterocytes from the mouse small intestine expressing TAg. Expression of TAg in the mouse intestine results in hyperplasia and dysplasia. Our analysis indicates that practically all gene expression regulated by TAg in enterocytes is dependent upon its binding and inactivation of the Rb-family proteins.
Publication Title
Simian virus 40 T-antigen-mediated gene regulation in enterocytes is controlled primarily by the Rb-E2F pathway.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Description
In cytotoxic T cells (CTL), Protein Kinase B /Akt is activated by the T cell antigen receptor (TCR) and the cytokine Interleukin 2 (IL2), in part by phosophorylation of Akt by Phospholipid dependent kinase 1 (PDK1).
Publication Title
Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Comparison of transcriptional profile of CD8 cytotoxic T lymphocytes terated with the mTORC1 inhibitor rapamycin or the mTOR inhibitor KU-0063794 and comparison with proteomic analysis.
Publication Title
The cytotoxic T cell proteome and its shaping by the kinase mTOR.
Sample Metadata Fields
Specimen part, Treatment
View Samples