Homeobox 60289 225993103 2008-07-16T10:42:28Z Boghog2 2428506 added TF abbreviation to navbox template A '''homeobox''' is a [[DNA sequence]] found within [[gene]]s that are involved in the regulation of development ([[morphogenesis]]) of [[animal]]s, [[fungus|fungi]] and [[plant]]s. [[Gene]]s that have a homeobox are called '''homeobox genes''' and form the '''homeobox gene family'''. The most studied and the most conserved group of homeodomain protein are the [[Hox genes]], which control segmental patterning during development, however not all homeodomain proteins are Hox proteins. ==Discovery== They were discovered independently in [[1983]] by [[Walter Jakob Gehring]] and his colleagues at the [[University of Basel]], [[Switzerland]], and Matthew Scott and Amy Weiner, who were then working with [[Thomas Kaufman]] at [[Indiana University (Bloomington)|Indiana University]] in [[Bloomington, Indiana|Bloomington]].<ref>{{cite journal |journal=Nature |year=1984 |volume=308 |issue=5958 |pages=428–33 |title=A conserved DNA sequence in homoeotic genes of the Drosophila [[Antennapedia]] and [[bithorax]] complexes |author=McGinnis W |coauthors=Levine MS, Hafen E, Kuroiwa A, Gehring WJ |pmid=6323992 | doi = 10.1038/308428a0 }} </ref><ref>{{cite journal |journal=PNAS |year=1984 |volume=81 |issue=13 |pages=4115–9 |title=Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila |author=Scott MP |coauthors=Weiner AJ |pmid=6330741 | doi = 10.1073/pnas.81.13.4115 }} </ref> ==Homeodomain== A homeobox is about 180 [[base pair]]s long; it encodes a [[protein]] domain (the [[homeodomain]]) which can bind [[DNA]]. Homeobox genes encode [[transcription factor]]s which typically switch on cascades of other genes. The homeodomain binds DNA in a specific manner. However, the specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the [[promoter region]] of their target genes as complexes with other transcription factors, often also homeodomain proteins. Such complexes have a much higher target specificity than a single homeodomain protein. ==Hox genes==<!-- This section is linked from [[Snake]] --> {{Main|Homeotic genes}} Molecular evidence shows that some limited number of Hox genes have existed in the [[Cnidaria]] since before the earliest true [[Bilatera]], making these genes pre-[[Paleozoic]].<ref>{{cite journal| last = Ryan |first = Joseph F |coauthors = Maureen E. Mazza, Kevin Pang, David Q. Matus, Andreas D. Baxevanis, Mark Q. Martindale, John R. Finnertyl | title = Pre-Bilaterian Origins of the Hox Cluster and the Hox Code: Evidence from the Sea Anemone, Nematostella vectensis | journal = PLoS ONE | url = http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000153 | year = 2007 | volume = 2 | pages = e153 | doi = 10.1371/journal.pone.0000153 <!--Retrieved from URL by DOI bot--> | issue = 1 | date = 2007-01 | unused_data = |accessdate 2008-04-30}}</ref> They are essential metazoan genes as they determine the identity of embryonic regions along the anterio-posterior axis. In vertebrates the 4 paralogue clusters are partially redundant in function, but have also acquired several derived functions in particular HoxA and HoxD specify the segment identity along the [[Limb (anatomy)|limb]] axis. The main interest in this set of genes stems is their unique behaviour. They are mostly found clustered together and the order they are found generally matches the order of regions they affect and their timing, a phenomenon called [[collinearity]]. Due to this balance, generally, when one gene is lost the segment becomes a more anterior one, while a gain of function mutant (ectopic) will be more posterior, famous examples of these are [[Antennapedia]] and bithorax in Drosophila. ==Diversity== The homeobox genes were first found in the fruit fly ''[[Drosophila melanogaster]]'' and have subsequently been identified in many other species, from [[insect]]s to [[reptile]]s and [[mammal]]s. Homeobox genes were previously only identified in [[bilateria]]ns but recently, [[cnidaria]]ns have also been found to contain homeobox domains and the "missing link" in the evolution between the two has been identified. Homeobox genes have even been found in [[fungi]], for example the [[unicellular]] [[yeast]]s, and in plants. ===Plants=== The well known [[homeotic]] genes in plants ([[MADS-box]] genes) are not [[homology (biology)|homologous]] to Hox genes in animals. Plants and animals do not share the same homeotic genes, and this suggests that homeotic genes arose independently in the early evolution of animals and plants. ===Human genes=== Humans generally contain homeobox genes in four clusters: {| class="wikitable" | '''name''' || '''[[chromosome]]''' || '''gene''' |- | HOXA (or sometimes HOX1) - {{Gene|HOXA@}} || [[chromosome 7]] || [[HOXA1]], [[HOXA2]], [[HOXA3]], [[HOXA4]], [[HOXA5]], [[HOXA6]], [[HOXA7]], [[HOXA9]], [[HOXA10]], [[HOXA11]], [[HOXA13]] |- | HOXB - {{Gene|HOXB@}} || [[chromosome 17]] || [[HOXB1]], [[HOXB2]], [[HOXB3]], [[HOXB4]], [[HOXB5]], [[HOXB6]], [[HOXB7]], [[HOXB8]], [[HOXB9]], [[HOXB13]] |- | HOXC - {{Gene|HOXC@}} || [[chromosome 12]] || [[HOXC4]], [[HOXC5]], [[HOXC6]], [[HOXC8]], [[HOXC9]], [[HOXC10]], [[HOXC11]], [[HOXC12]], [[HOXC13]] |- | HOXD - {{Gene|HOXD@}} || [[chromosome 2]] || [[HOXD1]], [[HOXD3]], [[HOXD4]], [[HOXD8]], [[HOXC9]], [[HOXD10]], [[HOXD11]], [[HOXD12]], [[HOXD13]] |} There is also a "distal-less homeobox" family: [[DLX1]], [[DLX2]], [[DLX3]], [[DLX4]], [[DLX]], and [[DLX6]]. "HESX homeobox 1" is also known as [[HESX1]]. [[Short stature homeobox gene]] is also known as [[SHOX]]. also a home gene controls the diffirensation of cells and tissue in the embryo. ==Mutations== Mutations to homeobox genes can produce easily visible [[phenotype|phenotypic]] changes. Two examples of homeobox mutations in the above-mentioned fruit fly are legs where the antennae should be ([[antennapedia]]), and a second pair of wings. Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the [[evolution]] of segmented animals. Interestingly, there is one [[insect]] family, the [[Xyelidae|xyelid sawflies]], in which both the [[Antenna (biology)|antennae]] and mouthparts are remarkably leg-like in structure. This is not uncommon in arthropods as all arthropod appendages are homologous. ==Regulation== The regulation of Hox genes is highly complex and involves reciprocal interactions, mostly inhibitory. [[Drosophila]] is known to use the [[Polycomb-group proteins|Polycomb]] and [[Trithorax]] Complexes to maintain the expression of Hox genes after the down-regulation of the pair-rule and gap genes that occurs during larval development. [[Polycomb-group proteins]] can silence the HOX genes by modulation of [[chromatin]] structure.<ref name= Portoso >{{cite book |chapterurl=http://www.horizonpress.com/rnareg|author= Portoso M and Cavalli G|year=2008|chapter=The Role of RNAi and Noncoding RNAs in Polycomb Mediated Control of Gene Expression and Genomic Programming|title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity|publisher=Caister Academic Press|id=[http://www.horizonpress.com/rnareg ISBN 978-1-904455-25-7]}}</ref> ==See also== *[[Evolutionary developmental biology]] *[[Body plan]] ==References== <references/> * {{cite book | author=Lodish et al | year=2003 | title=Molecular Cell Biology | edition=5th Edition |location=New York | publisher=W.H. Freeman and Company | id=ISBN 0-7167-4366-3}} *{{cite journal |journal=Gene |year=2007 |month=Jan |volume=387 |issue=1-2 |pages=21–30 |title=Missing link in the evolution of Hox clusters |author=Ogishima S |coauthors=Tanaka H. |pmid=17098381 | doi = 10.1016/j.gene.2006.08.011 }} ==External links== * [http://homeodb.cbi.pku.edu.cn/ Zhong YF, Butts T, Holland PWH, 2008. HomeoDB: a database of homeobox genes diversity] * [http://www.homeobox.cjb.net/ Homeodomain Resources provided by Thomas R. Bürglin] * [http://www.hhmi.org/genesweshare/b120.html Discovering the Homeobox] * {{MeshName|Homeobox}} {{Transcription factors|g3}} [[Category:Genes]] [[Category:Evolution]] [[Category:Developmental biology]] [[Category:Protein domains]] [[Category:Transcription factors]] [[ar:علبة مثلية]] [[de:Homöobox]] [[es:Homeobox]] [[fr:Homéoboîte et homéodomaine]] [[ja:ホメオボックス]] [[lt:Homeozinis genas]] [[nl:Homeobox]] [[pl:Geny homeotyczne]] [[pt:Homeobox]] [[zh:同位序列]]