Russell Karen, Emes Richard, Horrocks Paul
Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST5 5BG, UK.
School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, LE12 5RD, UK.
Parasit Vectors. 2015 Feb 5;8:81. doi: 10.1186/s13071-015-0701-0.
Over 2700 genes are subject to stage-specific regulation during the intraerythrocytic development of the human malaria parasite Plasmodium falciparum. Bioinformatic analyses have identified a large number of over-represented motifs in the 5' flanking regions of these genes that may act as cis-acting factors in the promoter-based control of temporal expression. Triaging these lists to provide candidates most likely to play a role in regulating temporal expression is challenging, but important if we are to effectively design in vitro studies to validate this role.
We report here the application of a repeated search of variations of 5' flanking sequences from P. falciparum using the Finding Informative Regulatory Elements (FIRE) algorithm.
Our approach repeatedly found a short-list of high scoring DNA motifs, for which cognate specific transcription factors were available, that appear to be typically associated with upregulation of mRNA accumulation during the first half of intraerythrocytic development.
We propose these cis-trans interactions may provide a combinatorial promoter-based control of gene expression to complement more global mechanisms of gene regulation that can account for temporal control during the second half of intraerythrocytic development.
超过2700个基因在人类疟原虫恶性疟原虫的红细胞内发育过程中受到阶段特异性调控。生物信息学分析已经在这些基因的5'侧翼区域鉴定出大量过度富集的基序，这些基序可能在基于启动子的时间表达控制中作为顺式作用因子。对这些列表进行分类以提供最有可能在调节时间表达中发挥作用的候选者具有挑战性，但如果我们要有效地设计体外研究来验证这一作用则很重要。
我们在此报告使用发现信息性调控元件（FIRE）算法对恶性疟原虫5'侧翼序列变异进行重复搜索的应用。
我们的方法反复发现了一份高分DNA基序的简短列表，对于这些基序有同源特异性转录因子可用，这些基序似乎通常与红细胞内发育前半段期间mRNA积累的上调相关。
我们提出这些顺式-反式相互作用可能提供基于启动子的基因表达组合控制，以补充更全局的基因调控机制，这些机制可以解释红细胞内发育后半段期间的时间控制。
