Yin-yang 1 and Glucocorticoid Receptor Participate in the Stat5-mediated Growth Hormone Response of the Serine Protease Inhibitor 2.1 Gene

Abstract

A growth hormone-inducible nuclear factor complex (GHINF), affinity-purified using the growth hormone response element (GHRE) from the promoter of rat serine protease inhibitor 2.1, was found to contain Stat5a and -5b, as well as additional components. The ubiquitous transcription factor yin-yang 1 (YY1) is present in GHINF. An antibody to YY1 inhibited the formation of the GHINF⅐GHRE complex in an electrophoretic mobility shift assay. Furthermore, Stat5 was co-immunoprecipitated from rat hepatic nuclear extracts with antibodies to YY1. An examination of the GHRE shows that, in addition to two ␥-activated sites, it contains a putative YY1 binding site between the two ␥-activated sites, overlapping them both. Mutation of this putative YY1 site results in a decrease of GHINF⅐GHRE complex formation in an electrophoretic mobility shift assay and a corresponding decrease in growth hormone (GH) response in functional assays. The glucocorticoid receptor was also present in GHINF, and Stat5 co-immunoprecipitates with glucocorticoid receptor in hepatic nuclear extracts from rats treated with GH. GH activation of serine protease inhibitor 2.1 requires the unique sequence of the GHRE encompassing the recognition sites of several transcription factors, and the interaction of these factors enhances the assembly of the transcription complex.

Th2 Cell-Selective Enhancement of HumanIL13Transcription byIL13-1112C>T, a Polymorphism Associated with Allergic Inflammation

“…In view of the dual role of YY1 in transcriptional regulation, two models may explain the role of YY1 in the increased activity of the IL13-1112T allele in Th2 cells. Both YY1 and STAT proteins may act cooperatively as transcriptional activators, as reported for YY1 and STAT5b binding to the serine protease inhibitor 2.1 gene (27). Alternatively, STAT binding to the IL13-1112 region may repress transcription, as reported for the human IL4 promoter (25), and YY1 may relieve STAT-mediated repression by displacing STATs or recruiting STAT corepressors.…”

Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription

“…At present, we know little about the assembly of transcriptional cofactors at either site, although in preliminary studies we find that acetylation of core histones accompanies GH-induced binding of Stat5b to HS7 (data not shown). CBP, p300 (41), SRC-1 (42), Nmi (43), and the glucocorticoid receptor (44,45) are among several characterized Stat5-binding proteins, yet none have been demonstrated to physically interact with the IGF-I locus on chromatin, or to play a role in GH-stimulated IGF-I gene transcription. Third, do additional GH response elements exist in the IGF-I gene?…”

The role of STAT proteins in growth hormone signaling

“…In the spi 2.1 promoter, STAT5 has been shown to associate with the glucocorticoid receptor (GR) and YY1 (Bergad et al, 2000). In addition, ®ve C/EBP sites have been identi®ed in the spi 2.1 promoter (LeCam et al, 1994), one of which coincides with GLE1 and is essential for GH-dependent enhancer function (LeCam et al, 1994).…”