Single-stranded DNA-binding proteins regulate the abundance and function of the LIM-homeodomain transcription factor LHX2 in pituitary cells.

Cai Y, Xu Z, Nagarajan L, Brandt SJ
Biochem Biophys Res Commun. 2008 373 (2): 303-8

PMID: 18565323 · PMCID: PMC2496924 · DOI:10.1016/j.bbrc.2008.06.027

A family of single-stranded DNA-binding proteins (or SSBPs) has been shown to augment the function of LIM-homeodomain (LIM-HD) transcription factors in embryogenesis by interaction with LIM domain-binding protein-1 (LDB1). No DNA-binding complex has been described, however, containing a LIM-HD protein, LDB1, and SSBP, and the mechanism by which SSBPs affect LIM-HD function had not been elucidated. Through use of electrophoretic mobility shift, antibody supershift, and ChIP analyses, we show that an Lhx2-Ldb1-Ssbp3 complex binds a specific element in the Lhx2 target gene Cga (encoding the alpha subunit of glycoprotein hormones) in the alphaT3-1 pituitary cell line. Using overexpression and knockdown approaches, we demonstrate that SSBP3 inhibits Lhx2 and Ldb1 turnover, stimulates assembly of this DNA-binding complex, promotes its recruitment to the Cga promoter, and enhances Cga transcription. These studies provide novel insights into the regulation of pituitary gene expression and LIM-HD function more generally.

MeSH Terms (16)

Animals Base Sequence Cell Line Chromatin Immunoprecipitation DNA, Single-Stranded DNA-Binding Proteins Electrophoretic Mobility Shift Assay Gene Expression Regulation Glycoprotein Hormones, alpha Subunit Homeodomain Proteins LIM-Homeodomain Proteins LIM Domain Proteins Mice Pituitary Gland Promoter Regions, Genetic Transcription Factors

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