Transcript profiling of Elf5+/- mammary glands during pregnancy identifies novel targets of Elf5

• Published in: PloS one 2010-10, Vol.5 (10), p.e13150-e13150
• Main Authors: Rogers, Renee L, Van Seuningen, Isabelle, Gould, Jodee, Hertzog, Paul J, Naylor, Matthew J, Pritchard, Melanie A
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding sites; Blotting, Western; Breasts; Cell Biology; Cell Biology/Cell Signaling; Developmental Biology/Cell Differentiation; DNA Primers; DNA-Binding Proteins - genetics; Electrophoretic Mobility Shift Assay; Embryos; ETS protein; Female; Gene expression; Gene Expression Profiling; Glands; Haploinsufficiency; Kinases; Lactation; Mammary gland; Mammary glands; Mammary Glands, Animal - metabolism; Medical research; Mice; Mice, Inbred C57BL; Molecular modelling; Mucin; Oligonucleotide Array Sequence Analysis; Pregnancy; Promoter Regions, Genetic; RNA, Messenger - genetics; Rodents; Target recognition; Transcription Factors - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013150

Elf5, an epithelial specific Ets transcription factor, plays a crucial role in the pregnancy-associated development of the mouse mammary gland. Elf5(-/-) embryos do not survive, however the Elf5(+/-) mammary gland displays a severe pregnancy-associated developmental defect. While it is known that Elf5 is crucial for correct mammary development and lactation, the molecular mechanisms employed by Elf5 to exert its effects on the mammary gland are largely unknown. Transcript profiling was used to investigate the transcriptional changes that occur as a result of Elf5 haploinsufficiency in the Elf5(+/-) mouse model. We show that the development of the mouse Elf5(+/-) mammary gland is delayed at a transcriptional and morphological level, due to the delayed increase in Elf5 protein in these glands. We also identify a number of potential Elf5 target genes, including Mucin 4, whose expression, is directly regulated by the binding of Elf5 to an Ets binding site within its promoter. We identify novel transcriptional targets of Elf5 and show that Muc4 is a direct target of Elf5, further elucidating the mechanisms through which Elf5 regulates proliferation and differentiation in the mammary gland.