Acetylation and methylation in nuclear receptor gene activation.
Activation of hormone target genes requires chromatin remodeling and histone modifications. The properties of the two PRMT coactivators. PRMT1 and CARM1, are compared in Table I. One can envision many scenarios in which histone arginine methylation contributes to transcriptional regulation. For example, it could be analogous to histone H3 K4 methylation by Set9, which blocks the HDAC NuRD complex from association and simultaneously impairs Suv39 h 1-mediated methylation at K9 of H3 (H3-K9). As a result, H3 K4 methylation by Set9 potentiates transcriptional activation. Histone arginine methylation might also promote or antagonize other histone-modifying enzymes. It has been shown that PRMT1-methylated histone H4 becomes a better substrate for p300 and, conversely, the acetylated histones are poor substrates for methylation by PRMT1. As for CARM1, acetylation of multiple lysines within histone H3 facilitates arginine methylation of by CARM1. Since PRMT1 and CARM1 methylate H4 and H3 tails, respectively, and each contributes to activation of the nuclear receptor response, it implicates the "histone code" as the physical template of hormone signaling. However, it remains to be resolved whether p160 family coactivators simultaneously recruit CARM1 and PRMT1 to specific target genes, and the order of the series of modifications on individual histone tails in vivo. Time-course studies of [table: see text] cofactor recruitment by ChIPs will be necessary to decipher the modification patterns. Another useful approach to analyze the function of NR cofactors on target gene transcription is the chromatin-dependent in vitro transcription system. As increasing amounts of evidence indicate that one HAT can be acetylated by another HAT, or methylated by HMT, it would not be surprising that transcription factors and their coactivators are bona fide substrates for protein modification.
Xu
Wei
W
Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Cho
Helen
H
Evans
Ronald M
RM
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis; D051997:ADP-ribosyl Cyclase 1; D000107:Acetylation; D015703:Antigens, CD / Q000096:biosynthesis; D001671:Biochemistry / Q000379:methods*; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D002850:Chromatography, Gel; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D004586:Electrophoresis; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006657:Histones; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins; D008745:Methylation; D008956:Models, Chemical; D008958:Models, Molecular; D017830:Octoxynol / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D013379:Substrate Specificity; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014508:Urea / Q000494:pharmacology
D015703:Antigens, CD; D002843:Chromatin; D003432:Cross-Linking Reagents; D003902:Detergents; D006657:Histones; D008024:Ligands; D008562:Membrane Glycoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D014508:Urea; D017830:Octoxynol; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1