Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The role of unliganded thyroid hormone receptors (TRs) in human adipose derived stem cells (hADSC)

ABSTRACT: Analysis of change in transcriptosome after TRÎ± or TRÎ² knockdown in hADSC. Analysis of effects of siRNA transfection (siCtrl, siTRÎ±, siTRÎ² or siETV5) in hADSC at gene expression level.The hypothesis tested in the present study was that unliganded TRÎ± and TRÎ² have distinctive roles in these cells. Total RNA was obtained from hADSC, transfected with siCtrl, siTRÎ±, siTRÎ² or ETV5. siTRÎ±, siTRÎ² or siETV5 samples were compared to siCtrl samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Paul Webb

PROVIDER: E-GEOD-75692 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Ligand Independent and Subtype-Selective Actions of Thyroid Hormone Receptors in Human Adipose Derived Stem Cells.

Cvoro Aleksandra A Bajic Aleksandar A Zhang Aijun A Simon Marisa M Golic Igor I Sieglaff Douglas H DH Maletic-Savatic Mirjana M Korac Aleksandra A Webb Paul P

PloS one 20161012 10

Thyroid hormone (TH) receptors (TRs α and β) are homologous ligand-dependent transcription factors (TFs). While the TRs display distinct actions in development, metabolic regulation and other processes, comparisons of TRα and TRβ dependent gene regulation mostly reveal similar mechanisms of action and few TR subtype specific genes. Here, we show that TRα predominates in multipotent human adipose derived stem cells (hADSC) whereas TRβ is expressed at lower levels and is upregulated during hADSC d ...[more]

PMID: 27732649

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Project description:Estrogen receptorï? beta (ER beta) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER beta-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER beta regulates genes, we identified genes regulated by the unliganded and liganded forms of ER alpha and ER beta in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER alpha, whereas many genes were regulated by estradiol (E2). These results demonstrate ER alpha requires a ligand to regulate a single class of genes. In contrast, ER beta regulated three classes of genes. Class I genes were regulated primarily by unliganded ER beta. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER beta and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER beta regulates different classes of genes ChIP-seq was performed to identify ER beta binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER beta bound to all three classes of genes demonstrating that ER beta binding is not responsible for differential regulation of genes by unliganded and liganded ER beta. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and liganded forms of ER beta regulate three classes of genes by interacting with different transcription factors and coactivators. U2OS cell lines are stably transfected with a doxycycline-inducible ER alpha or beta. 18 samples are analyzed with triplicate for each of the 6 conditions. The 6 conditions include ER alpha transfected without doxycycline added, ER alpha transfected with doxycycline added, ER alpha transfected with doxycycline added and E2 treatment, ER beta transfected without doxycycline added, ER beta transfected with doxycycline added, and ER beta transfected with doxycycline added and E2 treatment.

Dataset Information

The role of unliganded thyroid hormone receptors (TRs) in human adipose derived stem cells (hADSC)

Publications

Ligand Independent and Subtype-Selective Actions of Thyroid Hormone Receptors in Human Adipose Derived Stem Cells.

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