[en] Pit-1, a member of the POU-homeo domain protein family, is one of the transcription factors responsible for anterior pituitary development and pituitary-specific gene expression. Here, we describe seven children with GH, PRL, and TSH deficiency from three, reportedly unrelated, Middle Eastern families, harboring a newly recognized Pro- > Ser recessive mutation in codon 239 of the Pit-1 gene. The mutated residue is located at the beginning of the second alpha-helix of the POU-homeodomain and is strictly conserved among all POU proteins. The Pro239Ser mutant binds DNA normally but is unable to stimulate transcription.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Pernasetti, Flavia; University of California
Milner, Robert DG
al Ashwal, Abdullah A Z; University of Minnesota
de Zegher, Francis; University of Minnesota
Chavez, Viviana M; University of Minnesota
Muller, Marc ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Martial, Joseph ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Language :
English
Title :
Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle Eastern children with growth hormone, prolactin, and thyrotropin deficiency
Publication date :
1998
Journal title :
Journal of Clinical Endocrinology and Metabolism
ISSN :
0021-972X
eISSN :
1945-7197
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
Ingraham HA, Albert VR, Chen R, et al. 1990 A family of POU-domain and Pit-1 tissue specific transcriptional activators in pituitary and neuroendocrine development. Annu Rev Physiol. 52:773-791.
Bodner M, Castrillo JL, Theill LE, Deerink T, Ellisman M, Karin M. 1988 The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell. 55:505-518.
Ingraham HA, Chen R, Mangalam HJ, et al. 1988 A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell. 55:519-529.
Nelson C, Albert VR, Elsholtz HP, Lu LI-W, Rosenfeld MG. 1988 Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science. 239:1400-1405.
Fox S, Jong MTC, Casanova J, Ye Z-S, Stanley F, Samuels HH. 1990 The homeodomain protein Pit-1/GHF-1 is capable of binding to and activating cell-specific elements of both growth hormone and prolactin gene promoters. Mol Endocrinol. 4:1069-1080.
Steinfelder HJ, Hauser P, Nakayama Y, et al. 1991 Thyrotropin-releasing hormone regulation of the human TSH-β expression: role of a pituitary specific transcription factor (Pit-1/GHF-1) and potential interaction with thyroid hormone-inhibitory element. Proc Natl Acad Sci USA. 88:3130-3134.
Steinfelder HJ, Radovick S, Wondisford FE. 1992 Hormonal regulation of the thyrotropin-b subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1. Proc Natl Acad Sci USA. 89:5942-5945.
Lemaigre FP, Peers B, Lafontaine DA, et al. 1989 Pituitary-specific factor binding to the human prolactin, growth hormone and placental lactogen genes. DNA. 8:149-159.
Theill LE, Castrillo JL, Wu D, Karin M. 1989 Dissection of functional domains of the pituitary-specific transcription factor GHF-1. Nature. 342:945-948.
Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG. 1990 Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene PIT1. Nature. 347:528-533.
Tatsumi K, Miyai K, Notomi T, et al. 1992 Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. Nat Genet. 1:56-58.
Radovick S, Nations M, Du Y, Berg LA, Weintraub BD, Wondisford FE. 1992 A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. Science. 257:1115-1118.
Pfaffle RW, DiMattia GE, Parks JS, et al. 1992 Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science. 257:1118-1121.
Ohta K, Nobukuni Y, Mitsubuchi H, et al. 1992 Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency. Biochem Biophys Res Commun. 189:851-855.
Cohen LE, Wondisford FE, Salvatoni A, et al. 1995 A "hot spot" in the Pit-1 gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates. J Clin Endocrinol Metab. 80:679-684.
de Zegher F, Pemasetti F, Vanhole C, Devlieger H, Van den Berghe G, Martial JA. 1995 The prenatal role of thyroid hormone evidenced by feto-maternal Pit-1 deficiency. J Clin Endocrinol Metab. 11:3127-3130.
Irie Y, Tatsumi K, Kusuda S, et al. 1995 Screening for Pit-1 abnormality by PCR direct sequencing method. Thyroid. 5:207-211.
Okamoto N, Wada Y, Ida S, et al. 1994 Monoallelic expression of normal mRNA in the PIT1 mutation heterozygotes with normal phenotype and biallelic expression in the abnormal phenotype. Hum Mol Genet. 3:1565-1568.
Irie Y, Tatsumi K, Ogawa M, et al. 1995 A novel E250X mutation of the Pit-1 gene in patient with combined pituitary hormone deficiency. Endocr J. 42:351-354.
Walsh PS, Metzger DA, Higushi R. 1991 Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques. 10:506-513.
Pernasetti F, Wera S, Belayew A, Martial JA. 1993 Cloning of a human GHF-1/Pit-1 cDNA variant. Nucleic Acids Res. 21:3584.
Voz ML, Peers B, Belayew A, Martial JA. 1991 Characterization of an unusual thyroid response unit in the promoter of the human placental lactogen gene. J Biol Chem. 266:13397-13408.
Ohta K, Nobukuni Y, Mitsubuchi H, et al. 1992 Characterization of the gene encoding human pituitary-specific transcription factor Pit-1. Gene. 122:387-388.
Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO. 1994 Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA binding modules. Cell. 77:21-32.
Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK. 1997 Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev. 11:198-212.
Richardson JS, Richardson DC. 1988 Amino acid preferences for specific locations at the ends of helices. Science. 240:1648-1652.
Liang J, Moey-Rowley S, Maurer RA. 1995 In vivo mutational analysis of the DNA binding domain of the tissue-specific transcription factor Pit-1. J Biol Chem. 270:25520-25525.
