title: MAF1 represses CDKN1A through a Pol III-dependent mechanism.
abstract: MAF1 represses Pol III-mediated transcription by interfering with TFIIIB and Pol III. Herein, we found that MAF1 knockdown induced CDKN1A transcription and chromatin looping concurrently with Pol III recruitment. Simultaneous knockdown of MAF1 with Pol III or BRF1 (subunit of TFIIIB) diminished the activation and looping effect, which indicates that recruiting Pol III was required for activation of Pol II-mediated transcription and chromatin looping. Chromatin-immunoprecipitation analysis after MAF1 knockdown indicated enhanced binding of Pol III and BRF1, as well as of CFP1, p300, and PCAF, which are factors that mediate active histone marks, along with the binding of TATA binding protein (TBP) and POLR2E to the CDKN1A promoter. Simultaneous knockdown with Pol III abolished these regulatory events. Similar results were obtained for GDF15. Our results reveal a novel mechanism by which MAF1 and Pol III regulate the activity of a protein-coding gene transcribed by Pol II.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Ling
authors.identifier: http://orcid.org/0000-0003-1897-9918
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yuan-Ching
authors.initials: YC
authors.lastname: Li
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Su
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Chiao
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: I-Hsuan
authors.identifier: http://orcid.org/0000-0002-6207-1299
authors.initials: IH
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ming-Ta
authors.initials: MT
authors.lastname: Hsu
mesh_terms: D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012320:RNA Polymerase III / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C520535:MAF1 protein, human; D012097:Repressor Proteins; D004247:DNA; D012320:RNA Polymerase III
keywords: CDKN1A; MAF1; Pol III; biochemistry; cell biology; human