Sun Bryan K, Boxer Lisa D, Ransohoff Julia D, Siprashvili Zurab, Qu Kun, Lopez-Pajares Vanessa, Hollmig S Tyler, Khavari Paul A
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA;
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA; Department of Biology, Stanford University, Stanford, California 94305, USA;
Genes Dev. 2015 Nov 1;29(21):2225-30. doi: 10.1101/gad.267708.115.
Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differentiating outer epidermis. CALML5 mRNA was up-regulated by the ZNF750 transcription factor and then stabilized by the long noncoding RNA TINCR. CALML5 knockout impaired differentiation, abolished keratohyalin granules, and disrupted epidermal barrier function. Mass spectrometry identified SFN (stratifin/14-3-3σ) as a CALML5-binding protein. CALML5 interacts with SFN in suprabasal epidermis, cocontrols 13% of late differentiation genes, and modulates interaction of SFN to some of its binding partners. A ZNF750-TINCR-CALML5-SFN network is thus essential for epidermal differentiation.
表皮祖细胞向外迁移伴随着数百个分化基因的诱导，但该过程所需的所有调节因子的身份尚不清楚。我们使用激光捕获显微切割技术，随后进行RNA测序，以确定钙调蛋白样5（CALML5）是分化外层表皮中富集程度最高的基因。CALML5 mRNA被ZNF750转录因子上调，然后被长链非编码RNA TINCR稳定。CALML5基因敲除会损害分化，消除透明角质颗粒，并破坏表皮屏障功能。质谱分析确定SFN（层粘连蛋白/14-3-3σ）为CALML5结合蛋白。CALML5在基底上层表皮中与SFN相互作用，共同控制13%的晚期分化基因，并调节SFN与其一些结合伙伴的相互作用。因此，ZNF750-TINCR-CALML5-SFN网络对表皮分化至关重要。
