PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing.
PRDI-BF1, the human ortholog of mouse Blimp-1, is a DNA-binding protein involved in postinduction repression of interferon-beta gene transcription in response to viral infection. PRDI-BF1 also has an essential function in driving terminal differentiation of B lymphocytes and therein silences multiple genes. Here we show PRDI-BF1 assembles silent chromatin over the interferon-beta promoter in the osteosarcoma cell line U2OS through recruitment of the histone H3 lysine methyltransferase G9a. G9a is recruited only when in a complex with PRDI-BF1. G9a catalytic activity is required for the accumulation of methylated histone H3 and transcriptional silencing mediated by PRDI-BF1 in vivo. This establishes a mechanism for the recruitment of G9a, the main mammalian euchromatic methyltransferase, and defines nonembryonic targets of G9a.
Department of Biochemistry and Molecular Biology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, MRC4East, Tampa, FL 33612, USA.
Ildikó
I
Gyory
Jian
J
Wu
György
G
Fejér
Edward
E
Seto
Kenneth L
KL
Wright
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D020868:Gene Silencing; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016899:Interferon-beta / Q000235:genetics; D046911:Macromolecular Substances; D008780:Methyltransferases / Q000378:metabolism*; D008969:Molecular Sequence Data; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011496:Protein Methyltransferases; D021381:Protein Transport; D012097:Repressor Proteins / Q000502:physiology*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D002843:Chromatin; D046911:Macromolecular Substances; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D016899:Interferon-beta; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase