title: Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in beta-cells.
abstract: MAPK pathways regulate transcription through phosphorylation of transcription factors and other DNA-binding proteins. In pancreatic beta-cells, ERK1/2 are required for transcription of the insulin gene and several other genes in response to glucose. We show that binding of glucose-sensitive transcription activators and repressors to the insulin gene promoter depends on ERK1/2 activity. We also find that glucose and NGF stimulate the binding of ERK1/2 to the insulin gene and other promoters. An ERK1/2 cascade module, including MEK1/2 and Rsk, are found in complexes bound to these promoters. These findings imply that MAPK-containing signaling complexes are positioned on sensitive promoters with their protein substrates to modulate transcription in situ in response to incoming signals.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lawrence
authors.forename: Kathleen
authors.initials: K
authors.lastname: McGlynn
authors.forename: Chunli
authors.initials: C
authors.lastname: Shao
authors.forename: Lingling
authors.initials: L
authors.lastname: Duan
authors.forename: Bashoo
authors.initials: B
authors.lastname: Naziruddin
authors.forename: Marlon F
authors.initials: MF
authors.lastname: Levy
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb