Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene

Abstract

Members of the HMG-I(Y) family of mammalian nonhistone proteins are of importance because they have been demonstrated to bind specifically to the minor groove of A.T-rich sequences both in vitro and in vivo and to function as gene transcriptional regulatory proteins in vivo. Here we report the cloning, sequencing, characterization and chromosomal localization of the human HMG-I(Y) gene. The gene has several potential promoter/enhancer regions, a number of different transcription start sites and numerous alternatively spliced exons making it one of the most complex nonhistone chromatin protein-encoding genes so far reported. The putative promoter/enhancer regions each contain a number of conserved nucleotide sequences for potential binding of inducible regulatory transcription factors. Consistent with the presence of these conserved sequences, we found that transcription of the HMG-I(Y) gene is inducible in human lymphoid cells by factors such as phorbol esters and calcium ionophores. Detailed sequence analysis confirms our earlier suggestion that alternative splicing of precursor mRNAs gives rise to the major HMG-I and HMG-Y isoform proteins found in human cells. Furthermore, the gene's exon-intron arrangement fully accounts for all of the previously cloned human HMG-I(Y) cDNAs (1,2). Also of considerable interest is the fact that each of the three different DNA-binding domain peptides present in an individual HMG-I(Y) protein is coded for by sequences present on separate exons thus potentially allowing for exon 'shuffling' of these functional domains during evolution. And, finally, we localized the gene to the short arm of chromosome 6 (6p) in a region that is known to be involved in rearrangements, translocations and other abnormalities correlated with a number of human cancers.

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

“…[20][21][22][23][24][25][26][27][28][29][30][31][32] The putative oncogene, HMGIY (high mobility group protein isoforms I and Y), localized to 6p21 has been proposed to play a role in the development of a number of these neoplasms. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] An identical t(17;17)(q12;p13) was seen in two previous studies. 7,9 Interestingly, an inversion of chromosome 17 [inv(17)(p13q11.2-12)] involving similar breakpoints was observed in case 37 of the present study (Figure 3).…”

Regulation of HMGIC expression: an architectural transcription factor involved in growth control and development

“…Besides the switch in mRNA isoforms, there was also a decrease in HMGIC mRNA levels and this seemed even more pronounced for HMGI(Y). Since it is known that HMGI(Y) is regulated by multiple promoters (Friedmann et al, 1993), the transcription initiation sites for the HMGIC mRNA isoforms were also determined as described in a section below. As might be expected, alternative promoter usage appeared to be responsible for these multiple mRNA isoforms.…”

HMGI-C and HMGI(Y) Immunoreactivity Correlates with Cytogenetic Abnormalities in Lipomas, Pulmonary Chondroid Hamartomas, Endometrial Polyps, and Uterine Leiomyomas and is Compatible with Rearrangement of the HMGI-C and HMGI(Y) Genes

“…They act as architectural transcription factors and are commonly expressed in embryonal cells Hirning-Folz et al, 1998), in transformed cells with a malignant phenotype Bussemakers et al, 1991;Giancotti et al, 1987;1989;Ram et al, 1993), and in a variety of human cancers (Bandiera et al, 1998;Chiappetta et al, 1995;1998;Fedele et al, 1996;Rogalla et al, 1997;Rommel et al, 1997;Tamimi et al, 1993). HMGI-C and HMGI(Y) genes are located at 12q15 and 6p21 (Friedmann et al, 1993), respectively. HMGI-C is not expressed in normal adult mouse (Manfioletti et al, 1991) or human tissues (Rogalla et al, 1996), whereas HMGI(Y) is only expressed at very low levels .…”