Signaling silence--breaking ground and spreading out

Abstract

Among the persistent mysteries in epigenetics are the criteria by which specific regions of the genome are chosen for deposition of distinguishing chromatin marks. Once a particular region is modified, will the newly acquired epigenetic state spill onto neighboring regions of the genome or be confined to tidy patches? The report by Henderson and Jacobsen in the the previous issue of Genes & Development (1597-1606) addresses these questions while providing insight into the utility of DNA methylation for a eukaryotic genome.

Figure 1.

A model for the acquisition and maintenance of epigenetic silencing at the SDC locus. The SDC upstream region contains seven tandem repeats (red triangles) that recruit DNA methylation via siRNA production. The silent transcription status of SDC in wild-type is accompanied by spreading of siRNAs and DNA methylation into the adjacent nonrepeated sequences (see yellow box). Establishing DNA methylation of the SDC tandem repeats requires the de novo methyltransferase DRM2 and siRNA machinery, including PolIVa, RDR2, and DCL3. DNA methylation of the repeats is maintained by CMT3, DRM2, KYP, and MET1. Spreading of DNA methylation and siRNA spreading into flanking nonrepeated sequences are independent phenomena: MET1 has a direct or indirect role in spreading of methylation of both CG and non-CG methylation; siRNA machinery is required for spreading of siRNA in a DNA methylation-independent process. However, it is not clear whether siRNA production from the tandem repeats and siRNA spreading outside of the repeats occur simultaneously or consecutively. (mCG) Methylated CG; (non-mCG) methylated non-CG; (PolIVa) DNA-dependent RNA polymerase IVa; containing NRPD1a and NRPD2a, (RDR2) RNA-DEPENDENT RNA POLYMERASE2, (DCL3) DICER-LIKE3; (CMT3) CHROMOMETHYLASE3; (DRM2) DOMAINS REARRANGED METHYLTRANSFERASE2; (KYP) KRYPTONITE; histone H3K9 methyltransferase; (MET1) METHYLTRANSFERASE1.