Suv39h1 links the SUMO pathway to constitutive heterochromatin.

The Suv39h lysine methyltransferases, known as key enzymes responsible for histone H3 lysine 9 methylation, are critical for heterochromatin protein 1 enrichment at constitutive heterochromatin. Our recent findings reveal a new role for the Suv39h1 paralog that links it to SUMO pathway function at constitutive heterochromatin.

The methyltransferase Suv39h1 links the SUMO pathway to HP1α marking at pericentric heterochromatin.

The trimethylation of histone H3 on lysine 9 (H3K9me3) - a mark recognized by HP1 that depends on the Suv39h lysine methyltransferases (KMTs) - has provided a basis for the reader/writer model to explain HP1 accumulation at pericentric heterochromatin in mammals. Here, we identify the Suv39h1 paralog, as a unique enhancer of HP1α sumoylation both in vitro and in vivo. The region responsible for promoting HP1α sumoylation (aa1-167) is distinct from the KMT catalytic domain and mediates binding to Ubc9.

An epigenetic silencing pathway controlling T helper 2 cell lineage commitment.

During immune responses, naive CD4+ T cells differentiate into several T helper (TH) cell subsets under the control of lineage-specifying genes. These subsets (TH1, TH2 and TH17 cells and regulatory T cells) secrete distinct cytokines and are involved in protection against different types of infection. Epigenetic mechanisms are involved in the regulation of these developmental programs, and correlations have been drawn between the levels of particular epigenetic marks and the activity or silencing of specifying genes during differentiation.

The SUMO protease SENP7 is a critical component to ensure HP1 enrichment at pericentric heterochromatin.

SUMOylation promotes targeting of HP1α to pericentric heterochromatin. Here we identify the SUMO-specific protease SENP7 in mouse as a maintenance factor for HP1α accumulation at this location. SENP7 interacts directly with HP1α, localizes at HP1-enriched pericentric domains and can deconjugate SUMOylated HP1α in vivo.

SUMOylation promotes de novo targeting of HP1α to pericentric heterochromatin.

HP1 enrichment at pericentric heterochromatin is considered important for centromere function. Although HP1 binding to H3K9me3 can explain its accumulation at pericentric heterochromatin, how it is initially targeted there remains unclear. Here, in mouse cells, we reveal the presence of long nuclear noncoding transcripts corresponding to major satellite repeats at the periphery of pericentric heterochromatin.

HP1alpha guides neuronal fate by timing E2F-targeted genes silencing during terminal differentiation.

A critical step of neuronal terminal differentiation is the permanent withdrawal from the cell cycle that requires the silencing of genes that drive mitosis. Here, we describe that the alpha isoform of the heterochromatin protein 1 (HP1) protein family exerts such silencing on several E2F-targeted genes. Among the different isoforms, HP1alpha levels progressively increase throughout differentiation and take over HP1gamma binding on E2F sites in mature neurons.

Mouse centric and pericentric satellite repeats form distinct functional heterochromatin.

Heterochromatin is thought to play a critical role for centromeric function. However, the respective contributions of the distinct repetitive sequences found in these regions, such as minor and major satellites in the mouse, have remained largely unsolved. We show that these centric and pericentric repeats on the chromosomes have distinct heterochromatic characteristics in the nucleus.

Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component.

Post-translational modification of histone tails is thought to modulate higher-order chromatin structure. Combinations of modifications including acetylation, phosphorylation and methylation have been proposed to provide marks recognized by specific proteins. This is exemplified, in both mammalian cells and fission yeast, by transcriptionally silent constitutive pericentric heterochromatin.