Department of Histology and Embryology, Shantou University Medical College, Shantou, Guangdong, China.
PeerJ. 2024 Oct 15;12:e18240. doi: 10.7717/peerj.18240. eCollection 2024.
The zinc finger protein CTCF is ubiquitously expressed and is integral to the regulation of chromatin architecture through its interaction with cohesin. Conversely, CTCFL expression is predominantly restricted to the adult male testis but is aberrantly expressed in certain cancers. Despite their distinct expression patterns, the cooperative and competitive mechanisms by which CTCF and CTCFL regulate target gene expression in spermatocytes and cancer cells remain inadequately understood. In this review, we comprehensively examine the literature on the divergent amino acid sequences, target sites, expression profiles and functions of CTCF and CTCFL in normal tissues and cancers. We further elucidate the mechanisms by which CTCFL competitively or cooperatively binds to CTCF target sites during spermatogenesis and carcinogenesis to modulate chromatin architecture. We mainly focus on the role of CTCFL in testicular and cancer development, highlighting its interaction with CTCF at CTCF binding sites to regulate target genes. In the testis, CTCF and CTCFL cooperate to regulate the expression of testis-specific genes, essential for proper germ cell progression. In cancers, CTCFL overexpression competes with CTCF for DNA binding, leading to aberrant gene expression, a more relaxed chromatin state, and altered chromatin loops. By uncovering the roles of CTCF and CTCFL in spermatogenesis and carcinogenesis, we can better understand the implications of aberrant CTCFL expression in altering chromatin loops and its contribution to disease pathogenesis.
锌指蛋白 CTCF 广泛表达，通过与黏连蛋白相互作用，成为染色质结构调节的重要组成部分。相反，CTCFL 的表达主要局限于成年雄性睾丸，但在某些癌症中异常表达。尽管它们的表达模式明显不同，但 CTCF 和 CTCFL 调节精母细胞和癌细胞中靶基因表达的合作和竞争机制仍未得到充分理解。在这篇综述中，我们全面研究了 CTCF 和 CTCFL 在正常组织和癌症中的不同氨基酸序列、靶位、表达谱和功能的文献。我们进一步阐明了 CTCFL 在精子发生和癌变过程中竞争或合作与 CTCF 靶位结合调节染色质结构的机制。我们主要关注 CTCFL 在睾丸和癌症发展中的作用，强调其与 CTCF 在 CTCF 结合位点的相互作用，以调节靶基因。在睾丸中，CTCF 和 CTCFL 合作调节睾丸特异性基因的表达，这些基因对于正常的生殖细胞发育至关重要。在癌症中，CTCFL 的过度表达与 CTCF 竞争 DNA 结合，导致异常基因表达、更松弛的染色质状态和改变的染色质环。通过揭示 CTCF 和 CTCFL 在精子发生和癌变中的作用，我们可以更好地理解异常 CTCFL 表达在改变染色质环及其对疾病发病机制的贡献。
