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


RESULTS
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.


CONCLUSIONS
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.
Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Clayton, Victoria, Australia. r.rogers@garvan.org.au
Renee L
RL
Rogers
Isabelle
I
Van Seuningen
Jodee
J
Gould
Paul J
PJ
Hertzog
Matthew J
MJ
Naylor
Melanie A
MA
Pritchard
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D020869:Gene Expression Profiling; D057895:Haploinsufficiency; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C500759:Elf5 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors