Conserved sequences across species have always provided valuable insights to improve our understanding on the human genome's entity and the interplay among different loci. Lymphoma/leukemia related factor (LRF) is encoded by ZBTB7A gene and belongs to an evolutionarily conserved family of transcription factors, implicated in vital cellular functions. The present data, demonstrating the wide-spread and the high overlap of the LRF/ZBTB7A recognition sites with genomic segments identified as CpG islands in the human genome, suggest that its binding capacity strongly depends on a specific sequence-encoded feature within CpGs. We have previously shown that de-methylation of the CpG island 326 lying in the ZBTB7A gene promoter is associated with impaired pharmacological induction of fetal hemoglobin in β-type hemoglobinopathies patients. Within this context we aimed to investigate the extent of the LRF/ZBTB7A conservation among primates and mouse genome, focusing our interest also on the CpG island flanking the gene’s promoter region, in an effort to further establish its epigenetic regulatory role in human hematopoiesis and pharmacological involvement in hematopoietic disorders. Comparative analysis of the human ZBTB7A nucleotide and amino acid sequences and orthologous sequences among non-human primates and mouse, exhibited high conservation scores. Pathway analysis, clearly indicated that LRF/ZBTB7A influences conserved cellular processes. These data in conjunction with the high levels of expression foremost in hematopoietic tissues, highlighted LRF/ZBTB7A as an essential factor operating indisputably during hematopoiesis.

跨物种的保守序列一直以来提供了宝贵的见识，可增进我们对人类基因组实体以及不同基因座之间相互作用的了解。淋巴瘤/白血病相关因子（LRF）由ZBTB7A基因编码，属于进化上保守的转录因子家族，与重要的细胞功能有关。目前的数据证明了LRF / ZBTB7A识别位点与人类基因组中被识别为CpG岛的基因组片段的广泛传播和高度重叠，表明其结合能力在很大程度上取决于CpGs中的特定序列编码特征。先前我们已经证明了ZBTB7A中CpG岛326的去甲基化基因启动子与β型血红蛋白病患者胎儿血红蛋白的药理学诱导作用减弱有关。在此背景下，我们旨在研究LRF / ZBTB7A在灵长类动物和小鼠基因组中的保守程度，我们的兴趣也集中在该基因启动子区域两侧的CpG岛上，以进一步确立其在人类造血和药理学中的表观遗传调控作用。参与造血系统疾病。非人灵长类动物和小鼠之间的人ZBTB7A核苷酸和氨基酸序列以及直系同源序列的比较分析显示出高的保守性得分。路径分析，清楚地表明LRF / ZBTB7A影响保守的细胞过程。这些数据与造血组织中最重要的高表达水平相结合，突显了LRF / ZBTB7A是造血过程中无可争议的重要因素。