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Functional Role of THRAP3 in Modulating Thyroid Hormone–Mediated Gene Networks in C2C12 Myotubes

ABSTRACT: Thyroid hormone (TH) secreted by the thyroid gland plays essential roles in regulating metabolism, development, and nervous system function. Thyroid hormone receptor-associated protein 3 (THRAP3) is a nuclear coactivator that interacts with the thyroid hormone receptor (TR) and facilitates target gene regulation through the mediator complex. Although this mechanism has been well studied in other tissues, the specific role of THRAP3 in skeletal muscle remains unclear. Here we investigated the function of THRAP3 in skeletal muscle using Thrap3 knockout (KO) C2C12 cells. Loss of THRAP3 significantly suppressed the expression of key myogenic regulatory factors, including Myod1, Mef2c, and myosin heavy chain genes, resulting in impaired myogenic differentiation and muscle diameter. Furthermore, we found that THRAP3 influences triiodothyronine (T3)-induced gene expression, suggesting that it cooperatively modulates thyroid hormone signaling in muscle cells. Taken together, our findings identify THRAP3 as a novel regulator of myogenesis and indicate that it supports T3 activity by coordinating thyroid hormone–responsive gene expression in skeletal muscle.

ORGANISM(S): Mus musculus

PROVIDER: GSE306461 | GEO | 2025/12/11

REPOSITORIES: GEO

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Project description:Thyroid hormone receptors (TRs) represent important regulators of development, homeostasis, cell proliferation and differentiation. Here we investigated the impact of thyroid hormone (T3) on growth and differentiation of human red blood cells. T3 was found to effectively accelerate differentiation of SCF/Epo dependent red cell progenitors in vitro concomitantly with inducing growth arrest. This T3 activity was further enhanced by 9-cis retinoic acid (9cRA) that activates retinoid X receptor (RXR), the obligate heterodimeric partner of TR. To identify molecular targets for T3 activity in red cells, we employed a genome wide approach with DNA microarrays. We demonstrate that T3 and 9cRA induces specific gene expression patterns of up-or down-regulated genes, including ALAD and GATA-2, respectively. This study also revealed gene clusters, indicating accelerated differentiation in response to treatment. Mining for T3 induced genes identified BTEB1 (KLF9) and GAR22 as TR target genes. BTEB1/ KLF9 (basic transcription element binding protein 1/ KrÃ¼ppel-like factor 9) is a known TR target gene. GAR22 (growth arrest specific 2 (GAS2)-related gene on chromosome 22), initially found as a putative tumor suppressor gene, was induced by T3 also in the presence of cycloheximide, identifying it as a direct target of TR. Thus, our study uncovers novel targets of TR action with a potential function in T3 induced differentiation and growth arrest of red cell progenitors. Experiment Overall Design: 13 hybridizations in two individual experiments. Experiment Overall Design: Experiment 1: Experiment Overall Design: 1_SCF/Epo, 1_Epo/insulin(8h), 1_Epo/insulin(24h), 1_Epo/insulin(48h) Experiment Overall Design: Experiment 2: Experiment Overall Design: 2_SCF/Epo, 2_Epo/insulin(8h), 2_Epo/insulin(24h), 2_Epo/insulin(48h) Experiment Overall Design: 2_Epo/insulin+T3(8h), 2_Epo/insulin+9cRA(8h) Experiment Overall Design: 2_Epo/insulin+T3+9cRA(8h), , 2_Epo/insulin+T3+9cRA(24h), 2_Epo/insulin+T3+9cRA(48h)

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Functional Role of THRAP3 in Modulating Thyroid Hormone–Mediated Gene Networks in C2C12 Myotubes

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