Patterns of Liver Gene Expression Governed by TRβ

Flores‐Morales, Amilcar; Gullberg, Hjalmar; Fernández, Leandro; Ståhlberg, Nina; Lee, Norman H.; Vennström, Björn; Norstedt, Gunnar

doi:10.1210/mend.16.6.0846

Cited by 83 publications

(50 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Flores-Morales et al recently performed microarray analyses of hepatic genes in wild-type and Thrb knockout mice that were treated with T 3 . They found that 155 hepatic genes were regulated after treatment for 2 h with T 3 in wild-type mice, whereas only 84 hepatic genes were regulated in Thrb knockout mice under the same conditions (Flores-Morales et al, 2002). They hypothesized that some of these effects could be due to Tr-β-isoform-specific effects.…”

Section: Transcription Patterns Of Thra and Thrb Knockout Micementioning

confidence: 99%

“…Recently, cDNA microarrays have been used to study the hormonal regulation of gene expression, including that by Trs (Meltzer, 2001;Feng et al, 2000;Miller et al, 2001;Flores-Morales et al, 2002). Previously, we used cDNA microarrays to study hepatic gene profiles in hypothyroid and hyperthyroid mice, and we identified more than 50 target genes, which are involved in a range of cellular pathways (Feng et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice

et al. 2003

View full text Add to dashboard Cite

Little is known about the overall patterns of thyroid hormone (Th)-mediated gene regulation by the main Th receptor (Tr) isoforms, Tr-α and Tr-β, in vivo. We used 48 complementary DNA microarrays to examine hepatic gene expression profiles of wildtype and Thra and Thrb knockout mice under different Th conditions: no treatment, treatment with 3,3',5-triiodothyronine (T 3 ), Th-deprivation using propylthiouracil (PTU), and treatment with a combination of PTU and T 3 . Hierarchical clustering analyses showed that positively regulated genes fit into three main expression patterns. In addition, only a subpopulation of target genes repressed basal transcription in the absence of ligand. Interestingly, Thra and Thrb knockout mice showed similar gene expression patterns to wild-type mice, suggesting that these isoforms co-regulate most hepatic target genes. Differences in the gene expression patterns of Thra/Thrb double-knockout mice and Th-deprived wild-type mice show that absence of receptor and of hormone can have different effects. This large-scale study of hormonal regulation reveals the functions of Th and of Tr isoforms in the regulation of gene expression patterns. EMBO reports 4, 581-587 (2003) doi:10.1038/sj.embor.embor862 In the absence of Th, Trs recruit co-repressor complexes (for example, nuclear corepressor (NCoR) and silencing mediator of Tr and retinoic acid receptor (Smrt)) that lead to the histone deacetylation of local chromatin in the promoter region, and decrease the basal transcription of positively regulated target genes (Burke & Baniahmad, 2000). In the presence of Th, Trs recruit co-activator complexes that contain the p160 steroidreceptor co-activator (SRC) family members and other cofactors that have histone acetyltransferase activity, as well as other complexes that can associate with the RNA polymerase II complex (Yen, 2001;Zhang & Lazar, 2000). The overall effect of these ligand-dependent interactions is to promote the transcriptional activation of positively regulated target genes. Trs also negatively regulate target genes, but the molecular mechanism by which they do this is poorly understood (Yen, 2001).Recent studies have shown that Thra and Thrb knockout mice have different phenotypes, and have also suggested that different Tr isoforms may have distinct roles (Flamant & Samarut, 2003;Forrest & Vennstrom, 2000). Two groups have generated Thra knockout mice that have distinct phenotypes (Flamant & Samarut, 2003;Forrest & Vennstrom, 2000). This was due to the targeting of different loci for homologous recombination, which resulted in the loss of different combinations of Tr-α isoforms. Thra knockout mice that lack all Tr-α isoforms (Thra 0/0 ), including short Tr-α isoforms that are generated by internal transcription initiation, are viable and fertile, and have a mild phenotype (Gauthier et al., 2001;Macchia et al., 2001).

show abstract

Section: Transcription Patterns Of Thra and Thrb Knockout Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Flores-Morales et al [45] verified the effect of T3 on liver in mice with a targeted mutation in the TRβ gene. In accordance with the results of Weitzel [49], they reported that T3 regulates the expressions of functionally different sets of genes in temporally distinct ways.…”

Section: Transcriptomic Analysis Pertaining To the Actions Of Thyroidmentioning

confidence: 98%

Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches

Silvestri¹,

Lombardi²,

Lange³

et al. 2014

Omics in Clinical Practice

View full text Add to dashboard Cite

Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an a priori definition of scope, and this gives sufficient leeway for investigators (a) to discern all at once a globally altered pattern of gene/protein expression and (b) to examine the complex interactions that regulate entire biological processes. Two popular platforms in "omics" are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state) in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity.

show abstract

“…This insulin-dependent phosphorylation allows for a switch of recruitment of NCoR between different groups of NRs and provides a mechanism for specific modulation of NR signaling depending on physiological conditions (fed vs fasted). While the effect of the S1460 phosphorylation on NCoR-TR interactions has not been studied yet, it could potentially also have important ramifications for TR signaling, as TH has been shown in different experimental paradigms to promote both lipid synthesis and fatty acid oxidation in the liver (Feng et al 2000, Flores-Morales et al 2002, Jackson-Hayes et al 2003, Oppenheimer et al 1991.…”

Section: Liver-specific Ncor Knockoutmentioning

confidence: 99%

Role of co-regulators in metabolic and transcriptional actions of thyroid hormone

Astapova¹

2016

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Thyroid hormone (TH) controls a wide range of physiological processes through TH receptor (TR) isoforms. Classically, TRs are proposed to function as tri-iodothyronine (T 3 )-dependent transcription factors: on positively regulated target genes, unliganded TRs mediate transcriptional repression through recruitment of co-repressor complexes, while T 3 binding leads to dismissal of co-repressors and recruitment of co-activators to activate transcription. Co-repressors and co-activators were proposed to play opposite roles in the regulation of negative T 3 target genes and hypothalamic-pituitary-thyroid axis, but exact mechanisms of the negative regulation by TH have remained elusive. Important insights into the roles of co-repressors and co-activators in different physiological processes have been obtained using animal models with disrupted co-regulator function. At the same time, recent studies interrogating genome-wide TR binding have generated compelling new data regarding effects of T 3 , local chromatin structure, and specific response element configuration on TR recruitment and function leading to the proposal of new models of transcriptional regulation by TRs. This review discusses data obtained in various mouse models with manipulated function of nuclear receptor co-repressor (NCoR or NCOR1) and silencing mediator of retinoic acid receptor and thyroid hormone receptor (SMRT or NCOR2), and family of steroid receptor co-activators (SRCs also known as NCOAs) in the context of TH action, as well as insights into the function of co-regulators that may emerge from the genome-wide TR recruitment analysis.

show abstract

Patterns of Liver Gene Expression Governed by TRβ

Cited by 83 publications

References 44 publications

Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice

Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice

Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches

Role of co-regulators in metabolic and transcriptional actions of thyroid hormone

Contact Info

Product

Resources

About