Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries

摘要: Heterochromatin spreading leads to the silencing of genes within its path, and boundary elements have evolved constrain such spreading. In fission yeast, heterochromatin at centromeres I III is flanked by inverted repeats termed IRCs, which are required for proper functions. However, mechanisms IRCs prevent unknown. Here, we identified Bdf2, homologous mammalian bromodomain extraterminal (BET) family double proteins involved in diverse types cancers, as a factor function IRCs. Bdf2 enriched through interaction with protein Epe1. The bromodomains recognize acetylated histone H4 tails antagonize Sir2-mediated deacetylation H4K16. Furthermore, abolishing H4K16 acetylation (H4K16ac) an H4K16R mutation promotes spreading, mimicking H4K16ac H4K16Q blocks Our results thus illustrate mechanism establishing chromosome boundaries specific sites recruitment that protects euchromatic modifications. They also reveal previously unappreciated cooperation H3K9 methylation regulate