Site-specific mutagenesis has not revealed any precise determinants for sequence specificity or lack of it within the ARID family. Most probably, this is determined by multiple interacting differences across the entire ARID structure. A similar situation appears to hold for the distinction between sequence-specific and sequence-non-specific DNA binding in high mobility group (HMG) domain proteins. HMG domain containing proteins bind DNA through contacts in the minor groove. They recognize DNA structures such as four-way junctions, distorted cisplatin-kinked DNA and supercoiled DNA, and generally have the ability to bend DNA. One HMG protein subfamily consists of transcription factors like LEF-1 (lymphoid enhancer factor-1) and SRY (mammalian sex determining gene) that bind sequence specifically to AT-rich sequences in enhancer and promoter regions. Members of this subfamily contain one copy of the HMG domain and are tissue specific. Another subfamily comprises chromosomal proteins such as HMG1 and HMG2 that bind DNA in a sequence-non-specific manner. These proteins generally contain two or more HMG domains (47,48). There is a high degree of sequence similarity and structural characteristics between the sequence-specific and the sequence-non-specific HMG
