Vomhof-DeKrey Emilie E, Umthun Josey, Basson Marc D
Departments of Surgery, Pathology, and Biomedical Sciences, University of North Dakota, Grand Forks, ND, USA.
PeerJ. 2020 Jan 28;8:e8461. doi: 10.7717/peerj.8461. eCollection 2020.
The Schlafen (Slfn) family proteins are important for regulation of cell growth, cell differentiation and cell cycle progression. We sought to distinguish Slfn family expression in Slfn3 knockout (KO) mice after RNA sequencing analysis of Slfn3KO vs. wildtype (WT) mice revealed varying expressions of Slfn family in ileal mucosa.
Quantitative PCR analysis of Slfn members was evaluated in ileal mucosa, thymus and spleen tissue since Slfn family members have roles in differentiating intestinal and immune cells.
Ileal mucosa of Slfn3KO mice displayed a decrease in Slfn3, 4, 8 and 9 while Slfn1 and 5 increased in mRNA expression vs. WT mice. Thymic tissue had a Slfn9 increase and a Slfn4 decrease while splenic tissue had a Slfn8 and Slfn9 increase in Slfn3KO mice vs. WT mice. These differential expressions of Slfn members could indicate a feedback regulatory mechanism within the Slfn family. Indeed, MATCH tool from geneXplain predicted that all Slfn members have regions in their promoters for the Kruppel-like factor-6 transcription factor. In addition, NFAT related factors, ING4, ZNF333 and KLF4 are also predicted to bind in up to 6 of the 8 Slfn promoters. This study further describes a possible autoregulatory mechanism amongst the Slfn family members which could be important in how they regulate the differentiation of various cell types.
施拉芬(Slfn)家族蛋白对细胞生长、细胞分化和细胞周期进程的调节至关重要。在对Slfn3基因敲除(KO)小鼠与野生型(WT)小鼠进行RNA测序分析后,我们发现回肠黏膜中Slfn家族存在不同表达,于是试图区分Slfn家族在Slfn3 KO小鼠中的表达情况。
由于Slfn家族成员在肠道和免疫细胞分化中发挥作用,因此对回肠黏膜、胸腺和脾脏组织中的Slfn成员进行了定量PCR分析。
与WT小鼠相比,Slfn3 KO小鼠的回肠黏膜中Slfn3、4、8和9的mRNA表达降低,而Slfn1和5升高。与WT小鼠相比,Slfn3 KO小鼠的胸腺组织中Slfn9升高,Slfn4降低,脾脏组织中Slfn8和Slfn9升高。Slfn成员的这些差异表达可能表明Slfn家族内部存在反馈调节机制。事实上,来自geneXplain的MATCH工具预测,所有Slfn成员在其启动子区域都有与Kruppel样因子6转录因子结合的区域。此外,还预测NFAT相关因子、ING4、ZNF333和KLF4可与8个Slfn启动子中的多达6个结合。本研究进一步描述了Slfn家族成员之间可能存在的自动调节机制,这可能对它们如何调节各种细胞类型的分化具有重要意义。