Sex comb on midleg homolog 1

The post-translational modifications of histones regulate many cellular processes such as transcription, replication, DNA repair, recombination, and chromosome segregation (Ehrenhofer-Murray, 2004). These covalent modifications are found predominantly on the N-terminal tails of the four core histones, although there are increasingly more examples of modifications within the central part of the histone called the histone fold domain (Dialynas et al., 2006). A large number of combinations of post-translational modifications are possible, including acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, ADP ribosylation, deimination, and proline isomerization (reviewed in Kouzarides 2007). There are a number of enzymes that bring about aforementioned modifications. However, the recognition of the modifications, recruitment of proteins which are capable of “reading” the histone marks and cause downstream effects are less studied.

Malignant Brain Tumor (MBT) domain is one of many protein domains that are able to recognize the histone modifications; recently it has been shown that methylated lysines on core histones is the primary target (Kim et al., 2006). The proteins that contain MBT repeats belong to the PcG family of proteins, which have been grouped together because of their putative role in maintaining transcriptional repression of homeotic genes during development (reviewed in Schuettengruber et al., 2007). The MBT modules range from two to four repeats, each domain encompassing close to 100 amino acids.

In human genome there are two proteins that contain two MBT repeats in tandem: SCML2 and SCMH1. The structure of MBT domains of SCML2 has been solved in 2003 (Sathyamurthy et al., 2003), and here we show the structure of two MBT domains of SCMH1 protein. Human SCMH1 was first identified in 1999 and in addition to two MBT domains, it also contains sterile alpha motif (SAM) domain at the C-terminus (Berger et al., 1999). SCMH1 maps to chromosome 1p34 and is expressed strongly in heart, muscle, and pancreas (Berger et al., 1999). The function of the protein is yet unknown. However, the crystal structure of two MBT domains shown here will help to elucidate mechanistic insights into recognition of histone modifications by MBT domains.