title: H4R3 methylation facilitates beta-globin transcription by regulating histone acetyltransferase binding and H3 acetylation.
abstract: Histone modifications play an important role in the process of transcription. However, in contrast to lysine methylation, the role of arginine methylation in chromatin structure and transcription has been underexplored. The globin genes are regulated by a highly organized chromatin structure that juxtaposes the locus control region (LCR) with downstream globin genes. We report here that the targeted recruitment of asymmetric dimethyl H4R3 catalyzed by PRMT1 (protein arginine methyltransferase 1) facilitates histone H3 acetylation on Lys9/Lys14. Dimethyl H4R3 provides a binding surface for P300/CBP-associated factor (PCAF) and directly enhances histone H3 acetylation in vitro. We show that these active modifications are essential for efficient interactions between the LCR and the beta(maj)-promoter as well as transcription of the beta-globin gene. Furthermore, knockdown (KD) of PRMT1 by RNA interference in erythroid progenitor cells prevents histone acetylation, enhancer and promoter interaction, and recruitment of transcription complexes to the active beta-globin promoter. Reintroducing rat PRMT1 into the PRMT1 KD MEL cells rescues PRMT1 binding, beta-globin transcription, and erythroid differentiation. Taken together, our data suggest that PRMT1-mediated dimethyl H4R3 facilitates histone acetylation and enhancer/promoter communications, which lead to the efficient recruitment of transcription preinitiation complexes to active promoters.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Bhavita
authors.initials: B
authors.lastname: Patel
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhou
authors.forename: Shermi
authors.initials: S
authors.lastname: Liang
authors.forename: River
authors.initials: R
authors.lastname: Ybarra
authors.forename: Yi
authors.initials: Y
authors.lastname: Qiu
authors.forename: Gary
authors.initials: G
authors.lastname: Felsenfeld
authors.forename: Jörg
authors.initials: J
authors.lastname: Bungert
authors.forename: Suming
authors.initials: S
authors.lastname: Huang
mesh_terms: D000107:Acetylation; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051548:Histone Acetyltransferases / Q000378:metabolism* / Q000502:physiology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism* / Q000502:physiology; D008745:Methylation; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D011484:Protein-Arginine N-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D055544:beta-Globins; D001120:Arginine; D000076983:Histone Methyltransferases; C546338:Prmt1 protein, mouse; D011484:Protein-Arginine N-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases