HMGN3a and HMGN3b, two protein isoforms with a tissue-specific expression pattern, expand the cellular repertoire of nucleosome-binding proteins

HMGN1 (HMG-14) and HMGN2 (HMG-17) are nuclear proteins that bind specifical ly to nucleosomes reduce the compactness of the chromatin fiber, and enhanc e transcription from chromatin templates. Here we report that many vertebra tes contain an additional type of HMGN protein named HMGN3 (Trip 7), The hu man HMGN3 gene is located on chromosome 6 and spans 32 kilobase pairs, whic h is nearly 10-fold longer than the closely related HMGN2 gene. However, th e intron/exon boundaries of the HMGN3 gene are identical to those of HMGN1 and HMGN2. Unique within the HMGN family, the HMGN3 transcript undergoes al ternative splicing and generates two different variants, HMGN3a and HMGN3b. The shorter variant, HMGN3b, arises from an additional splice site that tr uncates exon V and causes a frameshift. The resulting HMGN3b protein lacks the majority of the C-terminal chromatin-unfolding domain. Both splice vari ants are found in many vertebrates from frogs to man and are expressed in m any tissues. The pattern of tissue-specific expression differs considerably from those of HMGN1 and HMGN2 at both the mRNA and the protein level. Our results expand the multiplicity of the HMGN protein family and raise the po ssibility that these nucleosome-binding proteins function as co-activators in tissue-specific gene expression.