InterPro domain: IPR028941

This entry represents the WHIM2 domain found in diverse eukaryotic chromatin proteins, such as animal BAZ/WAL and BPTF proteins, plant RLT and MBD9, and yeast Itc1. This domain contains the D-TOX E motif (also known as the Williams-Beuren syndrome DDT (WSD) motif) that is conserved from yeasts to animals [ 1 , 2 , 3 ].

WHIM2 domain is a conserved alpha helical motif that along with the WHIM1 and WHIM3 motifs, and the DDT domain comprise an alpha helical module found in diverse eukaryotic chromatin proteins [ 4 ]. Based on the Ioc3 structure, this module is inferred to interact with nucleosomal linker DNA and the SLIDE domain of ISWI proteins [ 4 , 4 ]. The resulting complex forms a protein ruler that measures out the spacing between two adjacent nucleosomes [ 4 ]. The acidic residue from the GxD signature of WHIM2 is a major determinant of the interaction between the ISWI and WHIM motifs. The N-terminal portion of the WHIM2 motif also contacts the inter-nucleosomal linker DNA. The module shows a great domain architectural diversity and is often combined with other modified histone peptide recognizing and DNA binding domains, some of which discriminate methylated DNA [ 4 ].

1. The HARE-HTH and associated domains: novel modules in the coordination of epigenetic DNA and protein modifications. Cell Cycle 11, 119-31
2. Structure and mechanism of the chromatin remodelling factor ISW1a. Nature 472, 448-53
3. A comprehensive classification and evolutionary analysis of plant homeobox genes. Mol. Biol. Evol. 26, 2775-94