RESUMEN
Germ cell development in C. elegans requires that the X chromosomes be globally silenced during mitosis and early meiosis. We previously found that the nuclear proteins MES-2, MES-3, MES-4 and MES-6 regulate the different chromatin states of autosomes versus X chromosomes and are required for germline viability. Strikingly, the SET-domain protein MES-4 is concentrated on autosomes and excluded from the X chromosomes. Here, we show that MES-4 has histone H3 methyltransferase (HMT) activity in vitro, and is required for histone H3K36 dimethylation in mitotic and early meiotic germline nuclei and early embryos. MES-4 appears unlinked to transcription elongation, thus distinguishing it from other known H3K36 HMTs. Based on microarray analysis, loss of MES-4 leads to derepression of X-linked genes in the germ line. We discuss how an autosomally associated HMT may participate in silencing genes on the X chromosome, in coordination with the direct silencing effects of the other MES proteins.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriología , Regulación del Desarrollo de la Expresión Génica , Células Germinativas/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Cromosoma X/genética , Animales , Caenorhabditis elegans/enzimología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/análisis , Proteínas de Caenorhabditis elegans/genética , Embrión no Mamífero/enzimología , Desarrollo Embrionario/genética , Femenino , Silenciador del Gen , Células Germinativas/citología , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/análisis , N-Metiltransferasa de Histona-Lisina/genética , Histonas/metabolismo , Masculino , Meiosis/genética , Metilación , Mitosis/genética , Proteínas Nucleares/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas del Grupo Polycomb , Proteína Metiltransferasas , Transcripción Genética , Cromosoma X/metabolismoRESUMEN
The C. elegans proteins MES-2 and MES-6, orthologs of the Polycomb group (PcG) chromatin repressors E(Z) and ESC, exist in a complex with their novel partner MES-3. The MES system participates in silencing the X chromosomes in the hermaphrodite germline. Loss of maternal MES function leads to germline degeneration and sterility. We report here that the MES complex is responsible for di- and trimethylation of histone H3 Lys27 (H3-K27) in the adult germline and in early embryos and that MES-dependent H3-K27 marks are concentrated on the X's. Another H3-K27 HMT functions in adult somatic cells, oocytes, and the PGCs of embryos. In PGCs, the MES complex may specifically convert dimethyl to trimethyl H3-K27. The HMT activity of the MES complex appears to be dependent on the SET domain of MES-2. MES-2 thus joins its orthologs Drosophila E(Z) and human EZH2 among SET domain proteins known to function as HMTs (reviewed in ). Methylation of histones is important for long-term epigenetic regulation of chromatin and plays a key role in diverse processes such as X inactivation and oncogenesis. Our results contribute to understanding the composition and roles of E(Z)/MES-2 complexes across species.