Sander G R, Powell B C
Department of Animal Science, University of Adelaide, Australia.
Gene. 2004 Feb 18;327(1):107-16. doi: 10.1016/j.gene.2003.11.006.
HOXC-13 has an important role in controlling hair formation through regulating keratin differentiation-specific genes. In this study, we describe the isolation and characterisation of the Hoxc-13 gene from sheep wool follicles and its expression in the skin. We show that the gene organisation of ovine Hoxc-13 is similar to other homeobox genes of the Abd-B type I Homeobox class with two exons split by an intron next to the homeobox. The gene spans 7.5 kilobases (kb) and has a relatively large intron, which divides an open reading frame of 2361 nucleotides. The predicted ovine Hoxc-13 protein of 330 amino acids has over 97% sequence identity with the human and mouse proteins. A second novel transcript was identified, which could produce a truncated Hoxc-13 protein lacking 15 amino acids from the N-terminus. A positionally conserved Hoxc-13 binding site in the Hoxc-13 proximal promoters of sheep, human, mouse and newt suggests that Hoxc-13 expression is autoregulatory. Positionally conserved motifs for LEF-1 and Whn/Foxn1 suggest that Hoxc-13 may be a downstream target of these transcription factors known to regulate hair growth. In addition to expression in the follicle, we detected Hoxc-13 in cells of the blood sinus surrounding vibrissal follicles and in scattered cells in the upper dermis of the skin. Thus, in addition to a role in controlling transcription of hair keratins, Hoxc-13 may have other roles in skin function.
HOXC - 13通过调节角蛋白分化特异性基因在控制毛发形成中发挥重要作用。在本研究中,我们描述了从绵羊毛囊中分离和鉴定Hoxc - 13基因及其在皮肤中的表达。我们发现绵羊Hoxc - 13的基因结构与Abd - B型I类同源框的其他同源框基因相似,有两个外显子,被靠近同源框的一个内含子隔开。该基因跨度为7.5千碱基(kb),有一个相对较大的内含子,它将一个2361个核苷酸的开放阅读框分开。预测的330个氨基酸的绵羊Hoxc - 13蛋白与人和小鼠的蛋白具有超过97%的序列同一性。鉴定出了第二个新转录本,它可以产生一个从N端缺少15个氨基酸的截短型Hoxc - 13蛋白。在绵羊、人类、小鼠和蝾螈的Hoxc - 13近端启动子中一个位置保守的Hoxc - 13结合位点表明Hoxc - 13的表达是自我调节的。LEF - 1和Whn/Foxn1的位置保守基序表明Hoxc - 13可能是这些已知调节毛发生长的转录因子的下游靶点。除了在毛囊中的表达,我们在触须毛囊周围血窦的细胞以及皮肤上层真皮中的散在细胞中检测到了Hoxc - 13。因此,除了在控制毛发角蛋白转录方面的作用外,Hoxc - 13可能在皮肤功能中还有其他作用。