CFP-1 interacts with HDAC1/2 complexes in C. elegans development
CFP-1 interacts with HDAC1/2 complexes in C. elegans development
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DOI：
10.1111/febs.14833
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发表时间：
2019-07-01
期刊：
影响因子：
5.4
通讯作者：
Biro, Jonathan Joseph
中科院分区：
文献类型：
--
作者：
Pokhrel, Bharat;Chen, Yannic;Biro, Jonathan Joseph
CXXC指结合蛋白1（CFP-1）是哺乳动物和秀丽隐杆线虫中与非甲基化的富含CpG的启动子结合的进化上保守的蛋白。这种保守的表观遗传调节因子是COMPASS复合物的一部分，该复合物包含哺乳动物中的H3 K4 me 3甲基转移酶SET 1和C中的SET-2。优雅先前的研究表明CFP 1在胚胎干细胞分化和细胞命运特化中的重要性。然而，CFP 1的功能和作用机制在生物体水平上都没有得到很好的理解。在这里，我们使用了cfp-1（tm 6369）和set-2（bn 129）C。研究CFP-1在基因诱导和发育中的功能。我们描述了C。elegansCOMPASS突变体cfp-1（tm 6369）和set-2（bn 129），发现cfp-1和set-2在调节生物体的生育力和发育中起重要作用。此外，我们发现cfp-1和set-2都是H3 K4三甲基化所必需的，并且在热休克和盐诱导基因的表达中起抑制作用。有趣的是，我们发现cfp-1而不是set-2与组蛋白脱乙酰酶（HDAC 1/2）复合物发生遗传相互作用以调节生育力，这表明CFP-1在COMPASS复合物之外的功能。此外，我们发现cfp-1和set-2独立调节生物体的生育和发育。我们的研究结果表明，CFP-1基因与HDAC 1/2复合物相互作用，以调节生育能力，独立于其在COMPASS复合物中的功能。我们认为CFP-1可以与COMPASS复合物和/或HDAC 1/2以上下文依赖的方式合作。
CXXC finger binding protein 1 (CFP-1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in mammals and Caenorhabditis elegans. This conserved epigenetic regulator is part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET-2 in C. elegans. Previous studies have indicated the importance of CFP1 in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action of CFP1 is well understood at the organismal level. Here, we have used cfp-1(tm6369) and set-2(bn129) C. elegans mutants to investigate the function of CFP-1 in gene induction and development. We have characterised C. elegansCOMPASS mutants cfp-1(tm6369) and set-2(bn129) and found that both cfp-1 and set-2 play an important role in the regulation of fertility and development of the organism. Furthermore, we found that both cfp-1 and set-2 are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt-inducible genes. Interestingly, we found that cfp-1 but not set-2 genetically interacts with histone deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP-1 outside of the COMPASS complex. Additionally, we found that cfp-1 and set-2 independently regulate fertility and development of the organism. Our results suggest that CFP-1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within the COMPASS complex. We propose that CFP-1 could cooperate with the COMPASS complex and/or HDAC1/2 in a context-dependent manner.