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[edit | edit source]

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:
1. loss-of-function mutations - pre-recessive changes;
2. gain-of-function mutations - back-to-front changes.

NOVOTNÁ, Božena – MAREŠ, Jaroslav. Vývojová biologie pro mediky. 1. edition. Praha : Karolinum, 2005. pp. 99. ISBN 80-246-1023-X.