Transcription factors with a homeodomain

One of the most important types of TF (transcription factor) are homeodomain proteins.
 * contain a highly conserved homeodomain' composed of 60 amino acid residues, which include a DNA-binding helix-loop-helix motif. In addition, TFs may also contain other conserved sequences (e.g., Engrail genes, Lim genes, PAX genes, etc.).
 * the homeodomain is encoded by a sequence of 180 nucleotides - the homeobox'. These sequences were first observed in the Drosophila homeotic genes antennapedia and bithorax.
 * The Drosophila m. gene complex consists of 8 genes containing a homeobox localized in 2 clusters on 1 chormosome.
 * humans have 39 homologous homeobox genes - HOX' localized in 4 clusters on 4 different chromosomechromosomes.
 * genes are activated and expressed in a precise order in the direction 3´→5´ according to their position on the chromosome. This implies that in humans the 3´ -genes are expressed earlier and earlier than the 5´ -genes.

Functions of Hox genes

 * play an important role in craniocaudal body organization and differential (spatiotemporal) regulation of some important developmental genes.
 * Hox genes were originally thought to act only along the main body axis, but later it was shown that they are also expressed in specific non-axial structures of various organs (intestine, fingers, limbs), blood cells, sex organs, hair follicles.
 * regulation of Hox genes is complex, the main regulator is along the anteroposterior axis retinoic acid'. Also, after transcription, the mRNA of these genes can be inactivated by microRNAs.
 * Hox gene mutations lead to morphological changes in the segmented structure:
 * loss-of-function mutations - pre-recessive changes;
 * gain-of-function mutations - back-to-front changes.

Related articles

 * Genetic control of differentiation in ontogeny