title: The TRAP100 component of the TRAP/Mediator complex is essential in broad transcriptional events and development.
abstract: The multisubunit TRAP/Mediator complex is a mammalian counterpart of the yeast Mediator that shows diverse coactivation functions. Genetic ablation of the murine TRAP100 component of this complex has revealed that it is not essential for cell viability per se. However, null mutant mice die at an early developmental stage with severe malformations, and cultured TRAP100-deficient cells exhibit attenuated functions of a wide variety of transcriptional activators on ectopic reporters. The TRAP100-deficient TRAP/Mediator complex also lacks TRAP95 and TRAP150 beta/SUR2, which together with TRAP100 may form a submodule, and contains a reduced amount of SRB10/CDK8. Nevertheless, the residual complex shows unaltered binding both to RNA polymerase II and, with the exception of the oncoprotein E1A, to various activators. These findings suggest that TRAP/Mediator is broadly involved in transcription and that a TRAP100-containing submodule plays a secondary role, beyond primary activator interactions and RNA polymerase recruitment by the TRAP complex, in magnifying effects of activators on the general transcriptional machinery.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ito
authors.forename: Hirotaka J
authors.initials: HJ
authors.lastname: Okano
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005804:Genes, Lethal; D017930:Genes, Reporter; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D046911:Macromolecular Substances; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012319:RNA Polymerase II / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection
chemical_list: D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D046911:Macromolecular Substances; C538856:Med1 protein, mouse; C121184:Med24 protein, mouse; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D018167:Receptors, Calcitriol; D014157:Transcription Factors; D012319:RNA Polymerase II