title: Human mediator subunit MED26 functions as a docking site for transcription elongation factors.
abstract: Promoter-proximal pausing by initiated RNA polymerase II (Pol II) and regulated release of paused polymerase into productive elongation has emerged as a major mechanism of transcription activation. Reactivation of paused Pol II correlates with recruitment of super-elongation complexes (SECs) containing ELL/EAF family members, P-TEFb, and other proteins, but the mechanism of their recruitment is an unanswered question. Here, we present evidence for a role of human Mediator subunit MED26 in this process. We identify in the conserved N-terminal domain of MED26 overlapping docking sites for SEC and a second ELL/EAF-containing complex, as well as general initiation factor TFIID. In addition, we present evidence consistent with the model that MED26 can function as a molecular switch that interacts first with TFIID in the Pol II initiation complex and then exchanges TFIID for complexes containing ELL/EAF and P-TEFb to facilitate transition of Pol II into the elongation stage of transcription.
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Hidehisa
authors: H
authors: Takahashi
authors: Tari J
authors: TJ
authors: Parmely
authors: Shigeo
authors: S
authors: Sato
authors: Chieri
authors: C
authors: Tomomori-Sato
authors: Charles A S
authors: CA
authors: Banks
authors: Stephanie E
authors: SE
authors: Kong
authors: Henrietta
authors: H
authors: Szutorisz
authors: Selene K
authors: SK
authors: Swanson
authors: Skylar
authors: S
authors: Martin-Brown
authors: Michael P
authors: MP
authors: Washburn
authors: Laurence
authors: L
authors: Florens
authors: Chris W
authors: CW
authors: Seidel
authors: Chengqi
authors: C
authors: Lin
authors: Edwin R
authors: ER
authors: Smith
authors: Ali
authors: A
authors: Shilatifard
authors: Ronald C
authors: RC
authors: Conaway
authors: Joan W
authors: JW
authors: Conaway
mesh_terms: D049109:Cell Proliferation; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D056892:Mediator Complex; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C492155:MED26 protein, human; C489427:MYC protein, human; D056892:Mediator Complex; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D035602:Transcriptional Elongation Factors; D012319:RNA Polymerase II