Mammary cell-activating factor regulates the hormone-independent transcription of the early lactation protein (ELP) gene in a marsupial. (15th November 2016)

• Record Type: Journal Article
• Authors: Pharo, Elizabeth A.; Renfree, Marilyn B.; Cane, Kylie N.
• Is Part Of: Molecular and cellular endocrinology. Volume 436(2016)
• Page Start: 169
• Page End: 182
• Publication Date: 2016-11-15
• Subjects: MAF -- ETS -- C/EBP -- Mammary gland -- Colostrum trypsin inhibitor -- Kunitz; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.07.023
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The regulation of the tammar wallaby ( Macropus eugenii ) early lactation protein ( ELP ) gene is complex. ELP is responsive to the lactogenic hormones; insulin (I), hydrocortisone (HC) and prolactin (PRL) in mammary gland explants but could not be induced with lactogenic hormones in tammar primary mammary gland cells, nor in KIM-2 conditionally immortalised murine mammary epithelial cells. Similarly, ELP promoter constructs transiently-transfected into human embryonic kidney (HEK293T) cells constitutively expressing the prolactin receptor (PRLR) and Signal Transducer and Activator of Transcription (STAT)5A were unresponsive to prolactin, unlike the rat and mouse β-casein ( CSN2 ) promoter constructs. Identification of the minimal promoter required for the hormone-independent transcription of tammar ELP in HEK293Ts and comparative analysis of the proximal promoters of marsupial ELP and the orthologous eutherian colostrum trypsin inhibitor ( CTI ) gene suggests that mammary cell-activating factor (MAF), an E26 transformation-specific (ETS) factor, may bind to an AGGAAG motif and activate tammar ELP . Highlights: Early Lactation Protein ( ELP ) expression is temporal and mammary gland-specific. The ELP gene is unresponsive to lactogenic hormones in 2D cell culture. The tammar wallaby ELP promoter has two TATA boxes and transcription start sites. An ETS factor may regulate the hormone-independent transcription of ELP . ELP may also be regulated by NF-κB, C/EBP, AP2ɣ and chromatin conformation.