This SuperSeries is composed of the SubSeries listed below.
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators.
Specimen part, Cell line
View SamplesThe closely related transcription factors (TFs), estrogen receptors ER and ER, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing MCF-7 breast cancer cells with ER, ER, or both receptors as a model system to define the basis of differing response specification by related TFs, we show that these TFs and their key coregulators, SRC3 and RIP140, generate overlapping as well as unique chromatin-binding and transcription-regulating modules.
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators.
Specimen part, Cell line
View SamplesWe used microarrays to detail the global transcriptional response mediated by ERalpha or ERbeta to the phytoestrogen genistein in the MCF-7 human breast cancer cell model.
Estrogen Receptors alpha and beta as determinants of gene expression: influence of ligand, dose, and chromatin binding.
No sample metadata fields
View SamplesThe MCF-7 were infected with either control adenovirus expressing B-galactosidase (Ad) or adenovirus expressing ERB (AdERbeta) for 72 h. For knockdown of the endogenous ERa in MCF-7 cells, cells were treated with siRNA for 24h (AdERbeta+SiERalpha). Then cells were treated with Veh (0.1% EtOH), 10 nM E2 or 1 uM BEs (botanical extracts) for 24h. Overall design: Duplicate samples run; treatment after knockdown included a control treatment (V), estradiol (E2) or botanical extracts; genistein (Gen), S-equol, liquiritigenin (Liq)
Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens.
No sample metadata fields
View SamplesThere is great medical need for estrogens having favorable pharmacological profiles, supporting desirable activities for menopausal women such as metabolic and vascular protection but lacking stimulatory activities on the breast or uterus. Here, we report the development of structurally novel estrogens with favorable target tissue-selective estrogenic activity. Through a process of structural alteration of the hormone estradiol that preserves essential chemical and physical features of estradiol but greatly moderates its binding affinity for the estrogen receptors (ERs), we obtained Pathway Preferential Estrogens (PaPEs) capable of having interaction with ER that is sufficient to activate the extranuclear-initiated signaling pathway preferentially over the direct nuclear-initiated pathway. PaPE modulate a pattern of gene regulation and cellular and biological processes that result in essentially no stimulation of reproductive and mammary tissues and breast cancer cells, but have a favorable pattern of activity on metabolic tissues and the vasculature. The structural permutation process represents a novel approach to govern the balance in utilization of extranuclear vs. nuclear pathways of ER action to obtain tissue-selective/non-nuclear pathway-preferential estrogens, which should prove to be beneficial for postmenopausal hormone replacement. The approach may also have broad applicability for other members of the nuclear hormone receptor superfamily. Overall design: 24 samples; inhibitor and time course experiments
Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues.
No sample metadata fields
View SamplesDuring meiosis in yeast, global splicing efficiency increases. The mechanism for this is relief of competition for the splicing machinery by repression of intron-containing ribosomal protein genes (RPGs). Repression of RPGs with rapamycin also increases splicing efficiency in vegetative cells. Reducing levels of an RPG-dedicated transcription factor globally improves splicing and suppresses the temperature-sensitive growth defect of a spliceosome mutation. These results indicate that the spliceosome is limiting and pre-mRNAs compete with each other. Under these conditions, splicing efficiency of a given pre-mRNA therefore depends on both its concentration and affinity for the limiting splicing factor(s) as well as those of the competing pre-mRNAs. We propose that trans-competition control of splicing helps repress meiotic gene expression in vegetative cells, and promotes efficient meiosis. Competition between RNAs for a limiting factor may be a general condition important for function of a variety of post-transcriptional control mechanisms. Overall design: Splicing and gene expression profiles of 1) wild type yeast cells treated with rapamycin (2 biological replicates) relative to untreated cells and 2) prp4-1 pGAL-IFH1 (down-regulated expression of IFH1 transcription factor(specific for ribosomal protein genes)) relative to prp4-1 yeast.
Competition between pre-mRNAs for the splicing machinery drives global regulation of splicing.
Treatment, Subject
View SamplesAdjacent alternative 3’ splice sites, those separated by =18nt, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron''s 3'' end depends upon sequence elements that define the branchpoint, polypyrimidine tract and terminal AG dinucleotide. Starting with RNA-seq data from germline-enriched and somatic cell-enriched C. elegans samples, we identify hundreds of introns with adjacent alternative 3’ splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is mono-directional, with somatic cells preferring to splice at the distal 3'' splice site and germline cells showing a distinct shift towards usage of the adjacent proximal 3'' splice site. Splicing patterns in somatic cells follow consensus rules of 3’ splice site definition, using sites with a short stretch of pyrimidines and an AG dinucleotide. Splicing in germline cells occurs at proximal 3'' splice sites that frequently lack a polypyrimidine tract or, occasionally, the AG dinucleotide. We provide evidence that use of germline-specific proximal 3'' splice sites is conserved across Caenorhabditis species. We propose that divergent mechanisms exist between germline and somatic cells in determining an intron terminus at adjacent alternative 3’ splice sites. Overall design: Examination of alternative splicing changes between germline- and somatic-cell enriched samples as well as nonsense-mediated decay mutants.
Coordinated tissue-specific regulation of adjacent alternative 3' splice sites in C. elegans.
Specimen part, Cell line, Subject
View SamplesThe goal of the study was to compare gene expression of P0 wild-type and P0 Satb2-/- cortices. Total RNAs were isolated from P0 cortices dissected from wild-type and Satb2-/- mice (n=3 for each genotype), following Qiagen RNAeasy kit instruction.Sequence libraries were made following Illumina RNA TruSeq library preparation guide.The libaries were pair-end sequenced (50nt per end). Differentially expressed genes were identified by DESEQ. Overall design: Total RNAs were isolated from P0 cortices (3 control and 3 mutants), and sequenced on Illumina Genome Analyzer
Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Specimen part, Subject
View SamplesWhole transcriptome profiling (Illumina Microarray) of human ex vivo lymphocytes and monocytes, as well as of human monocyte-derived cells generated in vitro by activating CD14+ monocytes with MCSF, GMCSF or the combination of GMCSF and IL4
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Specimen part
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