PMID- 22167189 OWN - NLM STAT- MEDLINE DCOM- 20120409 LR - 20240321 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 287 IP - 8 DP - 2012 Feb 17 TI - REF4 and RFR1, subunits of the transcriptional coregulatory complex mediator, are required for phenylpropanoid homeostasis in Arabidopsis. PG - 5434-45 LID - 10.1074/jbc.M111.312298 [doi] AB - The plant phenylpropanoid pathway produces an array of metabolites that impact human health and the utility of feed and fiber crops. We previously characterized several Arabidopsis thaliana mutants with dominant mutations in REDUCED EPIDERMAL FLUORESCENCE 4 (REF4) that cause dwarfing and decreased accumulation of phenylpropanoids. In contrast, ref4 null plants are of normal stature and have no apparent defect in phenylpropanoid biosynthesis. Here we show that disruption of both REF4 and its paralog, REF4-RELATED 1 (RFR1), results in enhanced expression of multiple phenylpropanoid biosynthetic genes, as well as increased accumulation of numerous downstream products. We also show that the dominant ref4-3 mutant protein interferes with the ability of the PAP1/MYB75 transcription factor to induce the expression of PAL1 and drive anthocyanin accumulation. Consistent with our experimental results, both REF4 and RFR1 have been shown to physically associate with the conserved transcriptional coregulatory complex, Mediator, which transduces information from cis-acting DNA elements to RNA polymerase II at the core promoter. Taken together, our data provide critical genetic support for a functional role of REF4 and RFR1 in the Mediator complex, and for Mediator in the maintenance of phenylpropanoid homeostasis. Finally, we show that wild-type RFR1 substantially mitigates the phenotype of the dominant ref4-3 mutant, suggesting that REF4 and RFR1 may compete with one another for common binding partners or for occupancy in Mediator. Determining the functions of diverse Mediator subunits is essential to understand eukaryotic gene regulation, and to facilitate rational manipulation of plant metabolic pathways to better suit human needs. FAU - Bonawitz, Nicholas D AU - Bonawitz ND AD - Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-2063, USA. FAU - Soltau, Whitney L AU - Soltau WL FAU - Blatchley, Michael R AU - Blatchley MR FAU - Powers, Brendan L AU - Powers BL FAU - Hurlock, Anna K AU - Hurlock AK FAU - Seals, Leslie A AU - Seals LA FAU - Weng, Jing-Ke AU - Weng JK FAU - Stout, Jake AU - Stout J FAU - Chapple, Clint AU - Chapple C LA - eng GR - Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20111213 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Arabidopsis Proteins) RN - 0 (Membrane Proteins) RN - 0 (Organic Chemicals) RN - 0 (Pancreatitis-Associated Proteins) RN - 0 (Protein Subunits) RN - 0 (REF4 protein, Arabidopsis) RN - 0 (REG3A protein, human) RN - 0 (RNA, Messenger) SB - IM MH - Arabidopsis/anatomy & histology/genetics/*metabolism MH - Arabidopsis Proteins/chemistry/genetics/*metabolism MH - *Gene Expression Regulation, Plant MH - Homeostasis/*genetics MH - Membrane Proteins/chemistry/deficiency/genetics/*metabolism MH - Mutation MH - Organic Chemicals/*metabolism MH - Pancreatitis-Associated Proteins MH - Phenotype MH - Phylogeny MH - Protein Subunits/metabolism MH - RNA, Messenger/genetics/metabolism MH - Sequence Homology, Amino Acid MH - *Transcription, Genetic PMC - PMC3285322 EDAT- 2011/12/15 06:00 MHDA- 2012/04/10 06:00 PMCR- 2013/02/17 CRDT- 2011/12/15 06:00 PHST- 2011/12/15 06:00 [entrez] PHST- 2011/12/15 06:00 [pubmed] PHST- 2012/04/10 06:00 [medline] PHST- 2013/02/17 00:00 [pmc-release] AID - S0021-9258(20)61205-4 [pii] AID - M111.312298 [pii] AID - 10.1074/jbc.M111.312298 [doi] PST - ppublish SO - J Biol Chem. 2012 Feb 17;287(8):5434-45. doi: 10.1074/jbc.M111.312298. Epub 2011 Dec 13.