Alternative titles; symbols
HGNC Approved Gene Symbol: MED24
Cytogenetic location: 17q21.1 Genomic coordinates (GRCh38): 17:40,019,104-40,054,408 (from NCBI)
Nuclear hormone receptors regulate transcription in part by recruiting distinct transcription coregulatory complexes to target gene promoters. The thyroid hormone receptor-associated proteins (TRAPs) form a complex with the thyroid hormone receptor (TR) (see THRA, 190120) and markedly enhance TR-mediated transcription in vitro.
Nagase et al. (1995) cloned TRAP100, which they designated KIAA0130, from a myeloid cell line. TRAP100 encodes a deduced 989-amino acid protein that contains a P-loop predicted to be an ATP/GTP-binding site. Northern blot analysis revealed ubiquitous expression in all tissues examined.
Yuan et al. (1998) immunopurified TRAP100 within TR/TRAP protein complexes from thyroid hormone (T3)-treated HeLa cells. Peptide sequencing followed by database searching indicated identity with the protein encoded by KIAA0130. TRAP100 has a calculated molecular mass of 110 kD and contains a presumptive zinc finger in the N terminus, a putative ATP/GTP-binding site in the central region, and 6 dispersed LXXLL motifs, suggesting nuclear hormone receptor interaction. Northern blot analysis revealed ubiquitous expression with relative abundance in skeletal muscle, heart, and placenta.
Zhang and Fondell (1999) identified mouse Trap100 by screening a mouse EST database with human sequences. The mouse protein shares 91% sequence identity with human TRAP100, but lacks 50 amino acids in the N terminus and contains 7 LXXLL motifs. Northern blot analysis of mouse tissues revealed abundant expression in testis, heart, and brain, and relatively low expression in spleen, lung, and skeletal muscle.
By gel filtration of TR/TRAP complexes in the absence of T3 ligand, Yuan et al. (1998) determined that the association of TRAP100 within the complex was not dependent on ligand binding. In contrast to the in vitro results obtained with TRAP220 (604311), they found no direct binding between TRAP100 and the thyroid receptor. TRAP100 also showed only marginal interaction with the estrogen receptor (see ESR1, 133430), retinoid X receptor-alpha (RXRA; 180245), PPAR-alpha (PPARA; 170998), and PPAR-gamma (PPARG; 601487). Zhang and Fondell (1999) noted that although mouse Trap100 contains 7 LXXLL repeats, it fails to interact directly with TR and other nuclear hormone receptors in vitro. Instead, they found that Trap100 interacts and coprecipitates with Trap220, which directly binds TR, and the vitamin D receptor (VDR; 601769) in a ligand-dependent manner. They found that transient overexpression of Trap100 in mammalian cells further enhanced ligand-dependent transcription by both TR and VDR, suggesting a functional role for Trap100 in nuclear hormone receptor-mediated transactivation.
Hamilton et al. (2019) found that extracellular signal-regulated kinase (ERK; see ERK2, 176948) reversibly regulates transcription in embryonic stem cells by directly affecting enhancer activity without requiring a change in transcription factor binding. ERK triggers the reversible association and disassociation of RNA polymerase II (see 180660) and associated cofactors from genes and enhancers with the mediator component MED24 having an essential role in ERK-dependent transcriptional regulation. Though the binding of mediator components responds directly to signaling, the persistent binding of pluripotency factors to both induced and repressed genes marks them for activation and/or reactivation in response to fluctuations in ERK activity. Among the repressed genes are several core components of the pluripotency network that act to drive their own expression and maintain the embryonic stem cell state; if their binding is lost, the ability to reactivate transcription is compromised. Thus, as long as transcription factor occupancy is maintained, so is plasticity, enabling cells to distinguish between transient and sustained signals. If ERK signaling persists, pluripotency transcription factor levels are reduced by protein turnover, and irreversible gene silencing and commitment can occur.
Stumpf (2020) mapped the MED24 gene to chromosome 17q21.1 based on an alignment of the MED24 sequence (GenBank BC011375) with the genomic sequence (GRCh38).
Hamilton, W. B., Mosesson, Y., Monteiro, R. S., Emdal, K. B., Knudsen, T. E., Francavilla, C., Barkal, N., Olsen, J. V., Brickman, J. M. Dynamic lineage priming is driven via direct enhancer regulation by ERK. Nature 575: 355-360, 2019. [PubMed: 31695196] [Full Text: https://doi.org/10.1038/s41586-019-1732-z]
Nagase, T., Seki, N., Tanaka, A., Ishikawa, K., Nomura, N. Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 2: 167-174, 1995. [PubMed: 8590280] [Full Text: https://doi.org/10.1093/dnares/2.4.167]
Stumpf, A. M. Personal Communication. Baltimore, Md. 06/03/2020.
Yuan, C.-X., Ito, M., Fondell, J. D., Fu, Z.-Y., Roeder, R. G. The TRAP220 component of a thyroid hormone receptor-associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proc. Nat. Acad. Sci. 95: 7939-7944, 1998. Note: Erratum: Proc. Nat. Acad. Sci. 95: 14584 only, 1998. [PubMed: 9653119] [Full Text: https://doi.org/10.1073/pnas.95.14.7939]
Zhang, J., Fondell, J. D. Identification of mouse TRAP100: a transcriptional coregulatory factor for thyroid hormone and vitamin D receptors. Molec. Endocr. 13: 1130-1140, 1999. [PubMed: 10406464] [Full Text: https://doi.org/10.1210/mend.13.7.0295]