Specificity protein 1 (Sp1) plays role in regulating LIM homeodomain transcription factor Lhx4 gene expression.
Both Sp-family factor Specificity protein 1 (Sp1) and LIM homeodomain transcription factor Lhx4 are involved in regulating the development of pituitary gland and nervous system in mammals. Sp1 gene mutation results in death of mouse embryo around day 11 of gestation, and mouse anterior pituitary development is severely hypoplastic after Lhx4 mutation. While Sp1 interacts with the related Lhx3 gene it is unclear whether Sp1 and Lhx4 also interact to regulate their physiological functions. The present study demonstrates that Lhx4 promoter is TATA-less and GC-rich and these sequences are conserved in different species. We have shown using site-directed mutagenesis and the Dual-Glo Luciferase Assay System that within the -515 to +36bp basic activity regions of hLhx4 promoter the GC boxes were important for Sp1 regulation of the hLhx4 promoter. The electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments confirmed that Sp1 interacted with Lhx4 by directly binding to GC boxes located in Lhx4 promoter. We conclude Sp1 directly regulates Lhx4 gene expression.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Beijing 100094, People's Republic of China.
Shuqiang
S
Liu
Haoshu
H
Luo
Jiali
J
Liu
Alan S
AS
McNeilly
Sheng
S
Cui
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D018398:Homeodomain Proteins; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; C108538:Lhx4 protein, mouse; D016329:Sp1 Transcription Factor; D014157:Transcription Factors