Robust identification of placental PPARg target genes via mutliple PPARg-dependence criteria.
Placental PPARĪ³ regulates spatiotemporally diverse genes and a unique metabolic network.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesSohlh1 and Sohlh2 encode a germ cell-specific basic helix-loop-helix transcriptional regulator critical in spermatogonial differentiation. Seven-day-old Sohlh1 or Sohlh2 knockout and wild-type testes were arrayed on the Affy 430 2.0 platform.
No associated publication
Specimen part
View SamplesSohlh1 and Sohlh2 are germ cell-specific basic helix-loop-helix transcription factors critical in early folliculogenesis. We discovered that Sohlh1 and Sohlh2 knockout females lose oocytes after birth and few remains by postnatal day 14. Here, we show that many genes preferentially expressed in the oocytes are misregulated by Sohlh1 and/or Sohlh2 deficiency.
No associated publication
Specimen part
View SamplesSohlh1 and Sohlh2 are germ cell-specific basic helix-loop-helix transcription factors critical in early folliculogenesis. Differential genes expression by both Sohlh1 and Sohlh2 deficiency in mouse newborn ovaries was accessed using microarray. RNA samples from Sohlh1/ Sohlh2 double knockout and wild-type newborn ovaries were arrayed on the Illumina beadchip mouse WG-6 2.0.
No associated publication
Specimen part
View SamplesAbnormal activities of histone lysine demethylases (KDMs) and lysine deacetylases (HDACs) are associated with aberrant gene expression in breast cancer development. However, the precise molecular mechanisms underlying the crosstalk between KDMs and HDACs in chromatin remodeling and regulation of gene transcription are still elusive. In this study, we showed that treatment of human breast cancer cells with inhibitors targeting the zinc cofactor dependent class I/II HDACs, but not NAD+ dependent class III HDACs, led to significant increase of H3K4me2 which is a specific substrate of histone lysine-specific demethylase 1 (LSD1) and a key chromatin mark promoting transcriptional activation. We also demonstrated that inhibition of LSD1 activity by a pharmacological inhibitor, pargyline, or siRNA resulted in increased acetylation of H3K9 (AcH3K9). However, siRNA knockdown of LSD2, a homolog of LSD1, failed to alter the level of AcH3K9, suggesting that LSD2 activity may not be functionally connected with HDAC activity. Combined treatment with LSD1 and HDAC inhibitors resulted in enhanced levels of H3K4me2 and AcH3K9, and exhibited synergistic growth inhibition of breast cancer cells. Finally, microarray screening identified a unique subset of genes whose expression was significantly changed by combination treatment with inhibitors of LSD1 and HDAC. Our study suggests that LSD1 intimately interacts with histone deacetylases in human breast cancer cells. Inhibition of histone demethylation and deacetylation exhibits cooperation and synergy in regulating gene expression and growth inhibition, and may represent a promising and novel approach for epigenetic therapy of breast cancer.
Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells.
Specimen part, Cell line
View SamplesWe performed gene expression microarray to examine the potential effect that depletion of HDAC5 (an important HDAC isozyme) or LSD1 (an FAD-dependent histone lysine demethylase) has on the triple-negative breast cancer transcriptome.
HDAC5-LSD1 axis regulates antineoplastic effect of natural HDAC inhibitor sulforaphane in human breast cancer cells.
Specimen part, Cell line
View SamplesAbnormal activities of histone lysine demethylases (KDMs) are associated with aberrant gene expression in breast cancer development. However, the precise molecular mechanisms in chromatin remodeling and regulation of gene transcription are still elusive. In this study, we performed Gene Expression Microarray (HG-U133A_2) using RNA from the aggressive breast cancer cell line MDA-MB-231 expressing stable knockdown or overexpression of LSD2. The goal of this study is to identify genes and pathways differentially expressed in triple negative breast cancer cells with genetically modified LSD2 expression.
No associated publication
Cell line
View SamplesWith aging, significant changes in circadian rhythms occur, including a shift in phase toward a morning chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here we employed a previously-described time-of-death analyses to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex (Brodmanns areas (BA) 11 and 47). Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ~10% of detected transcripts (p<0.05). Using a meta-analysis across the two brain areas, we identified a core set of 235 genes (q<0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than one thousand genes (1186 in BA11; 1591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep and mood in later life.
Effects of aging on circadian patterns of gene expression in the human prefrontal cortex.
Sex, Age, Specimen part, Race
View SamplesImpairments in certain cognitive processes (e.g., working memory) are typically most pronounced in schizophrenia (SZ), intermediate in bipolar disorder (BP) and least in major depressive disorder (MDD).
Transcriptome Alterations in Prefrontal Pyramidal Cells Distinguish Schizophrenia From Bipolar and Major Depressive Disorders.
Specimen part
View Samples