Components of a Pathway Maintaining Histone Modification and Heterochromatin Protein 1 Binding at the Pericentric Heterochromatin in Mammalian Cells

Abstract

Heterochromatin is a higher order chromatin structure that is important for transcriptional silencing, chromosome segregation, and genome stability. The establishment and maintenance of heterochromatin is regulated not only by genetic elements but also by epigenetic elements that include histone tail modification (e.g. acetylation and methylation) and DNA methylation. Here we show that the p33ING1-Sin3-HDAC complex as well as DNA methyltransferase 1 (DNMT1) and DNMT1-associated protein 1 (DMAP1) are components of a pathway required for maintaining proper histone modification and heterochromatin protein 1 binding at the pericentric heterochromatin. p33ING1 and DMAP1 interact physically and co-localize to heterochromatin in the late S phase, and both are required for heterochromatin protein 1 binding to heterochromatin. Although the p33ING1-Sin3-HDAC and DMAP1-DNMT1 complexes are recruited independently to pericentric heterochromatin regions, they are both required for deacetylation of histones and methylation of histone H3 at lysine 9. These data support a cooperative model for histone deacetylation, methylation, and DNA methylation in maintaining pericentric heterochromatin structure throughout cell divisions.