Fig. 2

Histone modifications and DNA cooperate in re-shaping chromatin organization and regulating gene expression. a (left) De novo DNA methylation occurs on unmethylated DNA. It is catalyzed by the DNMT3, whose subunits can be positioned in proximity of their target sites through physical interaction with unmethylated H3K4. a (right) Maintenance DNA methylation occurs during the DNA replication and is catalyzed by the DNMT1. Uhrf1 and proliferating cell nuclear antigen (PCNA) associates to DNMT1 and recruit it to the replication fork, concentrating its activity on hemimethylated DNA. The Uhrf1 TTD domain interacts with H3K9me. This binding allows a faithful propagation of DNA methylation patterns throughout mitosis. b (top) HDAC and the transcription factor complex (TFC) can be recruited on sensitive promoters, leading to histone deacetylation. HMT-driven methylation of the histone tails causes tight wrapping of DNA around nucleosome cores and inhibition of gene expression. b (bottom) The accumulation of HAT-driven histone acetylation determines DNA relaxation around the nucleosomes surrounding HAT-sensitive promoters; this leads to increased transcription and gene expression. c Methylation of H3K9 plays a central role in non-DNA-dependent mechanisms of regulation of gene activity (top). Hsp90 has a strong effect on the histone code via stabilization of KDM4B, which demethylases H3K9 (middle). Non-coding RNAs alter the histone code through siRNA-dependent mechanisms that lead to direct competition between BORDERLINE ncRNAs and H3K9me for binding to the HP1 proteins, such as Swi6. This occurs at heterochromatin/euchromatin boundary sites and counteracts the spreading of heterochromatin into neighboring euchromatin (bottom). A acetyl groups, M methyl groups, HAT histone acetyltranferase, HDAC histone deacetylase, HMT histone methyltransferase