Nucleotide sequence of a mouse cDNA encoding the nonhistone chromosomal high mobility group protein-1 (HMG1)

The high mobility group (HMG) proteins are the major nonhistone components of chromatin (1). Among these, the HMG1 and HMG2 proteins are the most abundant; however, their precise function remains undefined. There are some indications for a putative role of HMG 1/2 in chromatin assembly (2), DNA replication (3) or even as general transcription factors for RNA polymerase II (4). There is a considerable body of recent literature showing similarity between particular transcription factors and HMG 1/2. The homologous regions of these proteins are known as HMG boxes. Among these factors are hUBF (human upstream binding factor) (5), SRY (mammalian testes-determining factor) (6), LEF-1 Gymphoid enhancer-binding factor 1) (7), TCF-1 (T cellspecific factor) (8) and their analogues in other species. The progress in the study of HMG box-containing proteins is in contrast with the unavailability of HMG1 sequencing data for such a widely used laboratory model as the mouse. There is also confusion in the available sequences, caused by the significant differences in the length of the 5' and 3' non-coding regions. We addressed this problem by cloning and sequencing mouse HMG1 cDNAs. We constructed a cDNA library into the lambdaZap vector (Stratagene Corp., La Jolla, CA) using mRNA isolated from the P19 line of embryonal carcinoma cells (9). The sequence was obtained from three distinct overlapping clones (1-793, 1-1229, 1176-2231) and both strands of the recombinant cDNAs were sequenced entirely. This is the longest available HMG1 cDNA sequence. The ORF (nucleotides 73—718) encodes a 215 amino acid-long protein. When compared to the published cDNA sequences of other species, the mouse sequence shows the strongest similarity with HMG1 cDNAs from other rodents (see table 1). Mammalian HMG1 proteins contain two HMG boxes (amino acid positions 9 9 0 and 95-173). The only differences at the protein level are localised outside of these boxes. On the contrary, nonmammalian HMG protein sequences are less conserved, as are the HMG box-containing transcription factors. This may be due to the fact that HMGs and HMG box-containing proteins share only the necessity to bind DNA, but differ significantly in the role and specificity of this binding. Our HMG1 recombinants could prove helpful for the expression of recombinant mouse HMG 1 protein and for further studies of its still unclear function.