Regulation of Chromatin Looping and Transcription by PRMT1 Mediated H4R3 Methylation.

Communication between distal enhancers and proximal promoters is critical in controlling proper transcription of genes. However, the functional link between certain histone modifications and the formation of long-range chromatin interactions involved in transcriptional activation remains unknown. In the globin locus, the b-globin genes are regulated by highly organized chromatin structure that juxtaposes the locus control region (LCR) located far upstream of the genes with the proximal b-major globin promoter (b^majpromoter). We report here that the localized asymmetric dimethylation of Arg3 at histone H4 tails (dimethyl H4R3) catalyzed by the methyltransferase PRMT1 is essential for establishing the long-range chromatin interactions between the LCR and the b^maj-promoter and strongly correlates with the activation of adult b-globin gene transcription. In addition, dimethyl H4R3 potentiates the recruitment of histone acetyltransferases (HATs), CBP and PCAF, and is required for the establishment of subsequent histone acetylation at the globin locus. Suppression of PRMT1 activity disrupts the recruitment of transcription complexes, TBP and RNA polymerase II (RNA Pol II), at the active b-globin promoter, but not at the LCR. Taken together, our data implicate PRMT1-mediated dimethylation of H4R3 in the regulation of long-range enhancer/promoter communications, which are required for the efficient recruitment of transcription complexes to the active gene promoter.