Mechanism of chromatin segregation to the nuclear periphery in C. elegans embryos

Abstract

In eukaryotic organisms, gene regulation occurs in the context of chromatin. In the interphase nucleus, euchromatin and heterochromatin occupy distinct space during cell differentiation, with heterochromatin becoming enriched at the nuclear and nucleolar peripheries. This organization is thought to fine-tune gene expression. To elucidate the mechanisms that govern this level of genome organization, screens were carried out in C. elegans which monitored the loss of heterochromatin sequestration at the nuclear periphery. This led to the identification of a novel chromodomain protein, CEC-4 (Caenorhabditis elegans chromodomain protein 4) that mediates the anchoring of H3K9 methylation-bearing chromatin at the nuclear periphery in early to mid-stage embryos. Surprisingly, the loss of CEC-4 does not derepress genes found in heterochromatic domains, nor does it affect differentiation under standard laboratory conditions. On the other hand, CEC-4 contributes to the efficiency with which muscle differentiation is induced following ectopic expression of the master regulator, HLH-1. This is one of the first phenotypes specifically attributed to the ablation of heterochromatin anchoring.

Keywords: cell differentiation; heterochromatin; histone H3K9 methylation; nuclear organization; nuclear periphery.

Figure 1.

Anchoring chromatin to the nuclear periphery in C. elegans. In early embryos, CEC-4 is a H3K9 me1, me2 or me3 ligand that mediates anchoring to the nuclear periphery, without necessarily repressing transcription. The H3K9me-ligands, HPL-1, HPL-2 and LIN-61 mediate transcriptional repression by binding H3K9 methylation, but do not anchor chromatin. SET-25 recognizes the H3K9me3-containing chromatin that it creates and together with HP1 homologues and LIN-61, leads to repression. In differentiated cells alternative anchors may be present. Reprinted from Harr et al. © SM Gasser. Reproduced by permission of the authors. Permission to reuse must be obtained from the rightsholder.