Abd-A subfamily includes paralogous mouse/human genes Hox-2.4, -3.1 and -4.3. (See HOX Net)
Abd-B subfamily includes following paralogous mouse/human genes Hox-2.5, -1.7, -3.2 and -4.4. (See HOX Net)
In Drosophila the Antennapedia (Antp)-like HOM-class of homeo box genes controls the specification of segment phenotipes, according to their position along the anterior-posterior body axis. Four homologous clusters of genes, HOX-A, -B, -C, and -D, have been identified in mouse and human, with each cluster residing on a different chromosome (See HOX Net). The four HOX clusters likely arose from a common ancestor by duplication.
Antp-like subfamily consists of following paralogous human/mice genes Hox-2.2, -1.2, and -3.3. (See HOX Net)
Cdx-1 is murine analog of Drosophila caudal homeobox gene. Initially Cdx-1 become expressed in cells actively participating in the gastrulation process. Then this gene has been reported to be expressed during mid-embryogenesis (well after gastrulation) in the epithelial cells lining the intestine.
Dfd-subfamily contains following human/mice paralgous genes Hox-2.6, -1.4, and -4.2.
Double box genes are genes related to Hox genes and containing so called double box structures.
A murine even-skipped homologue, Evx1, is expressed during early murine embryogenesis and neurogenesis. There are two eve homeo box-homologs in murine genome: Evx1 and Evx2. Evx1, Evx2, eve and X-hox-3 constitute a family of related genes based on similar homeodomain sequences. In early post-implantation stages Evx1 transcripts are detected in primitive ectoderm, neuro-ectoderm and mesoderm at the posterior end of embryo, later - in neural tube Evx1 homeobox protein activates the cytotactin gene by specific binding to target site in its promoter: -CTGAGTCAT- -GACTCAGTA-
Binding site for glucocorticoids in gene promoter regions with consequence: -GAACANNNGTTC-
Binding site for heat shock element in gene promoter region with consequence: -CNNGAANNTTCNNG-
Hepatocyte Nuclear Factor-1 alfa (HNF-1alfa) is mammalian homeo domain containing protein must dimerize in order to bind to DNA.
Hox 11 is Antp-like Hox-gene, but distinct from previously identified HOX families. This gene located in human chromosome 10q24.
In mice and humans the homeo box-containing genes are clustered in four complex Hox loci (Hox families), distributed between four chromosomes. According to modern classification the families of the human homeo box-containing genes are localized in chromosomes 2, 7, 12 and 17 and are called Hox A, Hox B, Hox C, Hox D, respectively (Acampora et al., 1989; Boncinelli et al., 1989). In mice genotype Hox loci are shared between 6, 11, 15 and 2 chromosomes (Duboule et al., 1990, Ispisua-Belmonte et al., 1990) (See HOX Net).
Hox-1.3 binding site has consequence: -CYYNATTAKY-, where Y = T or C, K = T or G.
Hox-2.4 binding site has consequence: -ATTATTA- -TAATAAT-.
Hox-2.5 binding site has consequence: -ATTA- -TAAT-.
Antp (Drosophila) binding site: -ANNNNCATTA-.
Ftz, en, eve (Drosophila) binding site: -TCAATTAAAT-.
Mammalian Hox genes similarly located in the different clusters can be subgrouped by virtue of their homology to different Drosophila HOM-C genes. Members belonging to the same subfamily (paralogs) have similar anterior limits and patterns of expression. There are 13 subfamilies: Abd-B, Abd-A, Ubx, Antp, Scr, Dfd, Zen, pb, lab, and others. (See HOX Net)
These regions between promoters plus exons and introns of two neighbor genes is found to have multiple enhancers and other sites essential for gene regulation.
See: Hox-3.1/3.2 intergenic region and Hox-2.3/2.4 intergenic region. (See HOX Net)
Krox-20 gene is a segment-specific mammalian gene. The human homologue of Krox-20 was named EGR-2. The product of Krox-20 gene constitutes a sequence-specific DNA-binding transcription factor. This gene encodes a protein with three zinc fingers. Krox-20 protein binds in vitro to two specific DNA sites located upstream from the Hox-1.4 gene. The nucleotide sequence recognized by Krox-20 is closely related to Sp1 target sequence, which is consistent with similarity existing between the zinc fingers of the two proteins. There is at least one other transcription factor, Krox-24, with the same DNA specificity.
Lab subfamily consists of following mouse/human Hox genes: Hox-2.9; -1.6, and -4.9. (See HOX Net)
The Drosophila muscle segment homeo box (msh) gene contains a homeobox which is markedly divergent from that of any other characterized Drosophila genes, yet very similar to that of the mouse Hox-7.1 gene. Alignment of eight msh-like homeoboxes reveals extremely high levels of nt and aa sequence conservation between vertebrates, ascidian and Drosophila. Reconstruction of gene phylogenesis reveals that msh gene duplications preceded vertebrate radiation, and may have occurred concurrently with the origin of the vertebrate body plan. The Msh-like murine Hox-7.1 and Hox-8.1 is expressed in the surface ectoderm and in the optic vesicle before invagination occurs in regions corresponding to the prospective corneal epithelium and neural retina, respectively. Hox-7.1 is expressed after formation of the optic cup, marking the domain that will give rise to the ciliary body.
Msx-1 and Msx-2 are a novel homeo box gene subfamily. These genes are differentially expressed during early mesodermal patterning in mouse embryo. Msx-1 and msx-2 are expressed in the developing craniofacial complex, including the branchial arches, especially in regions of epithelial-mesenchymal organogenesis, including the developing tooth. These epithelial-mesenchymal interaction are required for msx genes expression.
Under conditions where Retinoic Acid Receptors (RARs), Retinoid X Receptors (RXRs), Thyroid Receptors (TR) bound poorly as homodimers to various response elements, strongly cooperative RAR-RXR and TR-RXR binding was observed. The binding efficiency was dependent on the sequence, relative orientation and spacing of the repeated motifs of response elements.
Pb subfamily consists of following mouse/human genes: Hox-2.8 (Hox-2H). (See HOX Net)
All of steriod, thyroid and retinoid response elements consist of the repetition of core motif, -AGG/TTCA- (or related sequence), in different configurations with respect to both the orientation (direct or inverse repetition) and the spacing of the two motifs. RARs have a preference for 5 bp spaced motifs, whereas TRs and RXRs preferentially recognize motifs separated by 4 bp and 1 bp respectively. Direct repeats are selective response elements for thyroid hormone, retinoic acid and vit.D receptors. Upon binding ligand, intracellular receptors for retinoic acid, thyroids and steroids act as dimeric transcription factors. Thyroid hormone response elements is identified that consist of a direct repeat, not a palindrome, of a half-sites. Unlike palindromic TREs, direct repeat TREs do not confers a retinoic acid response. The tandem TRE can be converted into retinoic acid response element by increasing the spacing between the half-sites by 1 nucleotide, and the resulting RARE is not longer a TRE.
Scr subfamily consists of following mouse/human Hox genes: Hox-2.1; -1.3; -3.4. (See HOX Net)
SIGNAL TRANSDUCTION AND REGULATION OF HOMEOBOX GENES BY POLYCOMB-GROUP GENES IN HUMANS (Oliver Hobert, Bahija Jallal, Axel Ullrich, Max-Planck-Institute for Biochemistry, Martinsried, Germany)
Sp1 protein activates transcription from many eucaryotic promoters. Sp1 protein binds to -GGGGCGGGGC- and closely related sequences. Sp1 factor The Sp1 protein activates a specific subset of promoters transcribed by RNA polymerase II in vertebrates. Sp1 binds to GGGGCGGGGC and closely related sequences, termed GC boxes. Transcriptional regulation by Sp1 depends on three zinc finger structures responsible for DNA binding and at least one of two glutamine-rich regions ("activator motifs"). Sp1 can act in vivo from enhancer sites that are distal to the promoter and exhibit synergistic interaction with promoter-proximal binding sites.
This superfamily of nuclear receptors include glucocorticoid receptors, thyroid receptors, retinoic acid receptors, retinoid X receptors. See also: "Nuclear receptors". SV40 enhancers SV40 enhancer has consensus sequence: -GTGGWWWG-, where W = T or A.
Pair of neighboring murine Hox genes (Hox-2.4 and 2.5) may define a molecular switch. Evidence suggests that similar switches may occur between other pairs of adjacent Hox genes. This may be a general property of adjacent Hox genes. The products of these two related Hox genes, which are located adjacent to each other in the Hox complex, can differently modulate transcription from the promoter of a Cell Adhesion Molecule (CAM) gene. Hox-2.4 protein is inhibitor, while Hox-2.5 protein is activator of N-CAM gene. N-CAM gene and cytotacin/tenascin (extracellular matrix proteins) has uncovered putative sequences for the binding of proteins encoded by homeobox genes: -ATTATTA-...-ATTA-
Binding site for thyroids in gene promoter regions with consequence: -GGTCATGACC-
Artificially created constructs from gene elements for investigation of mechanisms of gene expression.
Ubx subfamily consists of following mouse/human Hox genes: Hox-2.3; -1.1. (See HOX Net)
The sate of USF binding is -GGCCACGTGACC-. USF (MLTF) factor Adenovirus late transcription factor, USF, is a helix-loop-helix protein binding DNA as a dimer. The presence of two dimerization motifs (helix-loop-helix and leucine repeat) indicates its potential involvement in complex protein-protein interactions including heterodimerization with other h.-l.-h. proteins. The sate of USF binding is -GGCCACGTGACC-.
Zen subfamily consists of following mouse/human Hox genes: Hox-2.7; -1.5; -4.1. (See HOX Net)