Solution NMR Structure of the DNA-binding Domain from Scml2 (Sex Comb on Midleg-like 2). [Gene Regulation]

April 10th, 2014 by Bezsonova, I.

Scml2 is a member of the Polycomb group of proteins involved in epigenetic gene silencing. Human Scml2 is a part of a multi-subunit protein complex, PRC1 (Polycomb Repressive Complex 1), which is responsible for maintenance of gene repression, prevention of chromatin remodeling, preservation of the stemness of the cell and cell differentiation. While the majority of PRC1 subunits have been recently characterized, the structure of Scml2 and its role in PRC1-mediated gene silencing remain unknown. We have identified a conserved protein domain within human Scml2 and determined its structure by solution NMR spectroscopy. We named this module Scm-Like Embedded Domain, or SLED. Evolutionarily, the SLED domain emerges in the first multicellular organisms, consistent with the role of Scml2 in cell differentiation. Furthermore, it is exclusively found within the Scm-like family of proteins, often accompanied by MBT and SAM domains. The domain adopts a novel alpha/beta fold with no structural analogues found in the Protein Data Bank. We also examined the ability of the SLED domain to bind double-stranded DNA, and show that the isolated domain interacts with DNA in a sequence-specific manner. Since PRC1 complexes localize to the promoters of a specific subset of developmental genes in vivo, the SLED domain of Scml2 may provide an important link connecting the PRC1 complexes to their target genes.