KLF6 Human

KLF6 is widely expressed in several tissues, with the highest expression levels detected in the placenta . Other tissues with notable KLF6 expression include the spleen, thymus, prostate, testis, small intestine, and colon . The expression of KLF6 is crucial during trophoblast syncytialization, a process essential for placental development and pregnancy maintenance .

KLF6 plays a significant role as a transcriptional regulator of genes involved in placental differentiation and physiology, such as human β-chorionic gonadotropin (βhCG) and pregnancy-specific glycoprotein (PSG) genes . It has been shown to transactivate βhCG5, PSG5, and PSG3 gene promoters, indicating its importance in placental gene regulation . Additionally, KLF6 is involved in macrophage inflammatory and hypoxia responses, highlighting its role in immune response and tissue repair .

KLF6 functions by binding to specific DNA sequences through its zinc finger motifs, thereby regulating the transcription of target genes . The protein contains an N-terminal acidic domain, a Ser/Thr-rich region, and three zinc-finger motifs, which facilitate its interaction with other transcription factors and DNA . During trophoblast syncytialization, KLF6 expression peaks early and shows a preferential nuclear localization, correlating with enhanced expression of βhCG and PSG genes .

The regulation of KLF6 involves various factors, including its interaction with other transcription factors and response to environmental stimuli. For instance, in macrophages, KLF6 promotes inflammatory and hypoxic gene programs, which are essential for mounting an effective immune response . The deletion of KLF6’s Zn-finger DNA binding domain or mutation of its consensus binding site abolishes its transactivation ability, underscoring the importance of its zinc finger motifs in gene regulation .