Cell-type-selective induction of c-jun by TAF4b directs ovarian-specific transcription networks.
Cell-type-selective expression of the TFIID subunit TAF(II)105 (renamed TAF4b) in the ovary is essential for proper follicle development. Although a multitude of signaling pathways required for folliculogenesis have been identified, downstream transcriptional integrators of these signals remain largely unknown. Here, we show that TAF4b controls the granulosa-cell-specific expression of the proto-oncogene c-jun, and together they regulate transcription of ovary-selective promoters. Instead of using cell-type-specific activators, our findings suggest that the coactivator TAF4b regulates the expression of tissue-specific genes, at least in part, through the cell-type-specific induction of c-jun, a ubiquitous activator. Importantly, the loss of TAF4b in ovarian granulosa cells disrupts cellular morphologies and interactions during follicle growth that likely contribute to the infertility observed in TAF4b-null female mice. These data highlight a mechanism for potentiating tissue-selective functions of the basal transcription machinery and reveal intricate networks of gene expression that orchestrate ovarian-specific functions and cell morphology.
Geles
Kenneth G
KG
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, 16 Barker Hall, #3204, Berkeley, CA 94720, USA.
Freiman
Richard N
RN
Liu
Wei-Li
WL
Zheng
Shuang
S
Voronina
Ekaterina
E
Tjian
Robert
R
D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006062:Gonadotropins / Q000494:pharmacology; D006107:Granulosa Cells / Q000378:metabolism; D006736:Horses; D051379:Mice; D008817:Mice, Mutant Strains; D006080:Ovarian Follicle / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D006062:Gonadotropins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D035381:TATA-Binding Protein Associated Factors; C491103:Taf4b protein, mouse; D035362:Transcription Factor TFIID