Linking DNA replication to heterochromatin silencing and epigenetic inheritance

Abstract

Chromatin is organized into distinct functional domains. During mitotic cell division, both genetic information encoded in DNA sequence and epigenetic information embedded in chromatin structure must be faithfully duplicated. The inheritance of epigenetic states is critical in maintaining the genome integrity and gene expression state. In this review, we will discuss recent progress on how proteins known to be involved in DNA replication and DNA replication-coupled nucleosome assembly impact on the inheritance and maintenance of heterochromatin, a tightly compact chromatin structure that silences gene transcription. As heterochromatin is important in regulating gene expression and maintaining genome stability, understanding how heterochromatin states are inherited during S phase of the cell cycle is of fundamental importance.

Epigenetics in Intestinal Epithelial Cell Renewal

“…2) (Grunstein, 1997;Jaenisch and Bird, 2003;Kim and Kim, 2012). Due to their compact assembly, heterochromatin structures limit the access of transcriptional machinery to the more packaged DNA molecules which results in gene silencing (Li and Zhang, 2012). In contrast, euchromatin conformation is associated with the recruitment of transcription factors and RNA polymerase, resulting in gene expression ( Fig.…”

Interplay Between Histone H3 Lysine 56 Deacetylation and Chromatin Modifiers in Response to DNA Damage

“…The basic building block of chromatin is the nucleosome core particle composed of 147 bp of DNA wrapped around the surface of a protein octamer consisting of two molecules each of histones H2A, H2B, H3, and H4. During DNA replication, preexisting (old) histones are segregated onto sister chromatids, while new histones are deposited onto replicated DNA in order to restore normal nucleosome density on nascent sister chromatids (Ransom et al 2010;Li and Zhang 2012). In humans, newly synthesized histones H3 and H4 are acetylated on multiple residues within their N-terminal tails (Ruiz-Carrillo et al 1975;Benson et al 2006;Jasencakova et al 2010) and then are deacetylated following their incorporation into chromatin (Jackson et al 1976; …”

Preservation of Epigenetic Memory During DNA Replication

“…As an example of chromatin remodeling ATPases, Williams syndrome transcription factor (WSTF) forms a protein complex with the chromatin remodeling ATPase SMARCA5 (SWI-SNF related, matrix-associated, actindependent regulator of chromatin, subfamily a, member 5, also called SNF2H) and increases chromatin accessibility [17]. In addition to PCNA, the origin recognition complex (ORC) and DNA polymerases are known to maintain epigenetics in yeast and Drosophila but their roles in mammalian cells are far less clear than those of PCNA [18]. The parental octamers dissociate into two H2A-H2B dimers and a single (H3-H4) 2 tetramer, which are then transported across the replication fork and deposited onto the daughter duplexes.…”