HOXC

HOXC, or the homeobox C cluster, refers to one of the four paralogous HOX gene clusters in vertebrates. In humans, the HOXC cluster is located on chromosome 12 (12q13) and comprises multiple homeobox-containing genes arranged in a genomic sequence. The HOX genes encode transcription factors that regulate embryonic development and body plan along the anterior-posterior axis.

As with other HOX clusters, HOXC genes are expressed in patterns that reflect their genomic order, a property known as colinearity. In general, genes toward the 3' end of the cluster are active in more anterior regions, while more 5' genes contribute to posterior structures. The proteins produced by HOXC genes contain a homeodomain that enables DNA binding, and they commonly interact with cofactors such as PBX and MEIS to achieve DNA-binding specificity. Regulation of HOXC gene expression integrates multiple developmental signals, contributing to processes such as axial patterning, limb development, and organ formation.

The HOXC locus also contains the long noncoding RNA HOTAIR (HOX transcript antisense RNA), transcribed in antisense orientation from the HOXC region. HOTAIR can regulate gene expression in trans by guiding chromatin-modifying complexes, notably the Polycomb repressive complex 2 (PRC2) and LSD1, to the HOXD cluster, thereby influencing HOXD gene expression in development and cancer.

Evolutionarily, the HOXC cluster is conserved across vertebrates and participates in the broader organization and duplication history of HOX gene clusters. In model organisms such as mice, individual HOXC genes have defined roles in patterning and differentiation; for example, HOXC13 is linked to hair shaft formation.

Clinical and research significance arises from misregulation of HOXC genes or their regulatory networks, which can contribute to congenital malformations and various cancers.