Search

Heterochromatin is dynamically regulated during the cell cycle and in response to developmental signals. Recent findings from diverse systems suggest an extensive role for transcription in the assembly of heterochromatin, highlighting the emerging theme that transcription and noncoding RNAs can provide the initial scaffold for the formation of heterochromatin, which serves as a versatile recruiting platform for diverse factors involved in many cellular processes.

Summary Eukaryotic genome complexity necessitates boundary and insulator elements to partition genomic content into distinct domains. We show that inverted repeat ( IR ) boundary elements flanking the fission yeast mating-type heterochromatin domain contain B-box sequences, which prevent heterochromatin from spreading into neighboring euchromatic regions by recruiting transcription factor TFIIIC complex without RNA polymerase III (Pol III). Genome-wide analysis reveals TFIIIC with Pol III at all tRNA genes, many of which cluster at pericentromeric heterochromatin domain boundaries. However, a single tRNA phe gene with modest TFIIIC enrichment is insufficient to serve as boundary and requires RNAi-associated element to restrain heterochromatin spreading. Remarkably, we found TFIIIC localization without Pol III at many sites located between divergent promoters. These sites appear to act as chromosome-organizing clamps by tethering distant loci to the nuclear periphery, at which TFIIIC is concentrated into several distinct bodies. Our analyses uncover a general genome organization mechanism involving conserved TFIIIC complex.

Summary Transcriptional gene silencing (TGS) is the mechanism generally thought by which heterochromatin effects silencing. However, recent discovery in fission yeast of a cis -acting posttranscriptional gene-silencing ( cis -PTGS) pathway operated by the RNAi machinery at heterochromatin challenges the role of TGS in heterochromatic silencing. Here, we describe a multienzyme effector complex (termed SHREC) that mediates heterochromatic TGS in fission yeast. SHREC consists of a core quartet of proteins—Clr1, Clr2, Clr3, and Mit1—which distribute throughout all major heterochromatin domains to effect TGS via distinct activities associated with the histone deacetylase Clr3 and the SNF2 chromatin-remodeling factor homolog Mit1. SHREC is also recruited to the telomeres by multiple independent mechanisms involving telomere binding protein Ccq1 cooperating with Taz1 and the RNAi machinery, and to euchromatic sites, via mechanism(s) distinct from its heterochromatin localization aided by Swi6/HP1. Our analyses suggest that SHREC regulates nucleosome positioning to assemble higher-order chromatin structures critical for heterochromatin functions.