title: Cidea is an essential transcriptional coactivator regulating mammary gland secretion of milk lipids.
abstract: Adequate lipid secretion by mammary glands during lactation is essential for the survival of mammalian offspring. However, the mechanism governing this process is poorly understood. Here we show that Cidea is expressed at high levels in lactating mammary glands and its deficiency leads to premature pup death as a result of severely reduced milk lipids. Furthermore, the expression of xanthine oxidoreductase (XOR), an essential factor for milk lipid secretion, is markedly lower in Cidea-deficient mammary glands. Conversely, ectopic Cidea expression induces the expression of XOR and enhances lipid secretion in vivo. Unexpectedly, as Cidea has heretofore been thought of as a cytoplasmic protein, we detected it in the nucleus and found it to physically interact with transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) in mammary epithelial cells. We also observed that Cidea induces XOR expression by promoting the association of C/EBPβ onto, and the dissociation of HDAC1 from, the promoter of the Xdh gene encoding XOR. Finally, we found that Fsp27, another CIDE family protein, is detected in the nucleus and interacts with C/EBPβ to regulate expression of a subset of C/EBPβ downstream genes in adipocytes. Thus, Cidea acts as a previously unknown transcriptional coactivator of C/EBPβ in mammary glands to control lipid secretion and pup survival.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Wenshan
authors.initials: W
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Lv
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhang
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Xie
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Peng
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000502:physiology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006017:Glycolipids / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis; D007774:Lactation / Q000502:physiology; D066292:Lipid Droplets; D008055:Lipids / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008892:Milk / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D014968:Xanthine Dehydrogenase / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; C112510:Cidea protein, mouse; D006017:Glycolipids; D006023:Glycoproteins; D008055:Lipids; D014157:Transcription Factors; C110367:milk fat globule; D014968:Xanthine Dehydrogenase