LIM homeobox 1 is a protein that in humans is encoded by the LHX1 gene.[5] This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for control of differentiation and development of neural and lymphoid cells. It is also key in development of renal and urogenital systems and is required for normal organogenesis.[6] A similar protein in mice is an essential regulator of the vertebrate head organizer.[5]
The Lim gene family is a subfamily of homeobox genes.[7] The homeobox genes are essential in organizing the body plan of an organism and all contain the same conserved homeodomain of amino acids.[8] Evidence that Lim-1 is essential to a developing organism is its conservation throughout evolution and presence in a variety of organisms.[7] The Lim-1 gene encodes a transcription factor which binds to the DNA of specific genes and functions to produce the needed gene product for development of the organism.[9] Lim-1 is important during early molecular development and is required in both primitive streak-derived tissue and visceral endoderm of the early embryo for development of a head.[10] Studies done using mutant organisms without the Lim gene results in organisms that develop no head structure at all support the essential role of the Lim-1 gene in formation of the head.[11] This gene has also been shown to play a crucial role in the formation of the female reproductive tract.[9] The gene is expressed in the developing Müllerian duct of females, and when the gene is knocked out no reproductive tract forms.[9] Recent studies have shown that Lim-1 mutations may be one cause of the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.[12] MRKH is characterized by defective development, or absence, of the uterus and upper part of the vagina in women with normal ovaries and karyotype.[12]
Lim-1’s expression is controlled in part by the sonic hedgehog-Gli signaling pathway.[6] Recent studies in mice have shown that Lim-1 silencing halts tumor growth and impairs tumor cell movement via inhibition of protein expression involved in metastatic spread.[6] Therefore, in tumor cells Lim-1 acts as an oncogene.[6] Thus, targeting Lim-1 can be a potential cancer therapy. In addition, Lim-1 is important in rodent renal development.[13] Lim-1 deficiency results in development of multicystic kidney, whereas, its expression can contribute to pathogenesis of nephroblastomas.[13] Also, Lim-1 plays a role in embryonic retinal development.[14] Lim-1 expression affects differentiation and maintenance of horizontal cells located in the retinal, thus, it could serve as a marker in studies of horizontal cell specification.[14]
Lim-1 (Lhx1) functions as a transcription factor necessary for regulating the production of coupling factors required for proper communication between the neurons located in the part of the brain responsible for regulation of circadian rhythms called the suprachiasmatic nucleus (SCN).[15] In mouse studies where Lim-1 transcription was restricted at some point during development in utero, the individual units within the subject’s molecular clock functioned properly but were unable to work together.[15] Communication of these units is required to match their release of clock proteins which begin a transcription cascade of many other proteins that produce functional responses in tissues.[15] The cyclic pattern of these responses is due to the feedback of the clock proteins and consequent changes to this transcription cascade.[15] Reduced Lim-1 expression leads to inadequate levels of proteins such as Vasoactive Intestinal Polypeptide (VIP) that work to produce the neuron coordination required for a regulated circadian rhythm.[15] The lack of such coupling factors causes the circadian clock to not function properly because the units within the SCN cannot match their release of clock proteins, and therefore their transcriptional cascades of proteins that cause changes in arousal do not align.[15]
^ abcdDormoy, V.; et al. (2011). "LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma". Oncogene. 30 (15): 1753–1763. doi:10.1038/onc.2010.557. PMID 21132009.
^ abHobert, Oliver; Heiner Westphal (February 2000). "Functions of LIM-homeobox genes". Trends in Genetics. 16 (2): 75–83. doi:10.1016/S0168-9525(99)01883-1. PMID 10652534.
^Carlson BM (2009). Human Embryology and Developmental Biology. Philadelphia, PA: Mosby Elsevier. pp. 67–70. ISBN978-0-323-05385-3.
^ abcKobayashi A, Shawlot W, Kania A, Behringer RR (Feb 2004). "Requirement of Lim1 for female reproductive tract development". Development. 131 (3): 539–49. doi:10.1242/dev.00951. PMID 14695376.
^Shawlot W, Wakamiya M, Kwan KM, Kania A, Jessell TM, Behringer RR (Nov 1999). "Lim1 is required in both primitive streak-derived tissues and visceral endoderm for head formation in the mouse". Development. 126 (22): 4925–32. doi:10.1242/dev.126.22.4925. PMID 10529411.
^Bally-Cuif L, Boncinelli E (Feb 1997). "Transcription factors and head formation in vertebrates". BioEssays. 19 (2): 127–35. doi:10.1002/bies.950190207. PMID 9046242. S2CID 44679684.
^ abLedig S, Brucker S, Barresi G, Schomburg J, Rall K, Wieacker P (Sep 2012). "Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome". Human Reproduction. 27 (9): 2872–5. doi:10.1093/humrep/des206. PMID 22740494.
^ abGuertl B, Senanayake U, Nusshold E, Leuschner I, Mannweiler S, Ebner B, Hoefler G (2011). "Lim1, an embryonal transcription factor, is absent in multicystic renal dysplasia, but reactivated in nephroblastomas". Pathobiology. 78 (4): 210–9. doi:10.1159/000326769. PMID 21778788.
^ abLiu W, Wang JH, Xiang M (Mar 2000). "Specific expression of the LIM/homeodomain protein Lim-1 in horizontal cells during retinogenesis". Developmental Dynamics. 217 (3): 320–5. doi:10.1002/(SICI)1097-0177(200003)217:3<320::AID-DVDY10>3.0.CO;2-F. PMID 10741426.
^ abcdefHatori M, Gill S, Mure LS, Goulding M, O'Leary DD, Panda S (Jul 2014). "Lhx1 maintains synchrony among circadian oscillator neurons of the SCN". eLife. 3: e03357. doi:10.7554/eLife.03357. PMC4137275. PMID 25035422.
Bozzi F, Bertuzzi S, Strina D, Giannetto C, Vezzoni P, Villa A (Dec 1996). "The exon-intron structure of human LHX1 gene". Biochemical and Biophysical Research Communications. 229 (2): 494–7. doi:10.1006/bbrc.1996.1832. PMID 8954926.
Dong WF, Heng HH, Lowsky R, Xu Y, DeCoteau JF, Shi XM, Tsui LC, Minden MD (Jun 1997). "Cloning, expression, and chromosomal localization to 11p12-13 of a human LIM/HOMEOBOX gene, hLim-1". DNA and Cell Biology. 16 (6): 671–8. doi:10.1089/dna.1997.16.671. hdl:10722/44331. PMID 9212161.
Jurata LW, Pfaff SL, Gill GN (Feb 1998). "The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors". The Journal of Biological Chemistry. 273 (6): 3152–7. doi:10.1074/jbc.273.6.3152. PMID 9452425.
Ostendorff HP, Peirano RI, Peters MA, Schlüter A, Bossenz M, Scheffner M, Bach I (Mar 2002). "Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors". Nature. 416 (6876): 99–103. doi:10.1038/416099a. PMID 11882901. S2CID 4426785.
Phillips JC (2003). "Assignment of LHX1 to human chromosome bands 17q11.2-->q12 by use of radiation hybrid mapping and somatic cell hybridization". Cytogenetic and Genome Research. 97 (1–2): 140D. doi:10.1159/000064048. PMID 12438757.
April 13, 2023
lhx1, homeobox, protein, that, humans, encoded, gene, this, gene, encodes, member, large, protein, family, which, contains, domain, unique, cysteine, rich, zinc, binding, domain, encoded, protein, transcription, factor, important, control, differentiation, dev. LIM homeobox 1 is a protein that in humans is encoded by the LHX1 gene 5 This gene encodes a member of a large protein family which contains the LIM domain a unique cysteine rich zinc binding domain The encoded protein is a transcription factor important for control of differentiation and development of neural and lymphoid cells It is also key in development of renal and urogenital systems and is required for normal organogenesis 6 A similar protein in mice is an essential regulator of the vertebrate head organizer 5 LHX1IdentifiersAliasesLHX1 LIM 1 LIM1 LIM homeobox 1External IDsOMIM 601999 MGI 99783 HomoloGene 4068 GeneCards LHX1Gene location Human Chr Chromosome 17 human 1 Band17q12Start36 936 785 bp 1 End36 944 612 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 C 11 51 31 cMStart84 409 110 bp 2 End84 416 361 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incerebellumcerebellar cortexcerebellar hemispherekidneyhypothalamusright uterine tubesubstantia nigraprefrontal cortexleft uterine tubeganglionic eminenceTop expressed inhypoblastsuprachiasmatic nucleusconnecting tubulemesodermglomeruluscerebellar vermismammillary bodyneural tuberete testisproximal tubuleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionsequence specific DNA binding DNA binding transcription corepressor activity DNA binding transcription factor activity metal ion binding DNA binding transcription factor activity RNA polymerase II specific RNA polymerase II transcription regulatory region sequence specific DNA binding cis regulatory region sequence specific DNA bindingCellular componentintracellular anatomical structure nucleus protein containing complex transcription regulator complexBiological processpattern specification process pronephros development oviduct epithelium development cell differentiation renal system development ureteric bud development positive regulation of branching involved in ureteric bud morphogenesis mesonephric tubule development regulation of transcription DNA templated retina layer formation comma shaped body morphogenesis spinal cord association neuron differentiation embryonic pattern specification mesonephric duct development uterine epithelium development kidney development positive regulation of gastrulation vagina development metanephric glomerulus development cell cell signaling somite rostral caudal axis specification anatomical structure morphogenesis gastrulation with mouth forming second cerebellar Purkinje cell differentiation cerebellar Purkinje cell granule cell precursor cell signaling involved in regulation of granule cell precursor cell proliferation anatomical structure formation involved in morphogenesis head development metanephric renal vesicle morphogenesis transcription by RNA polymerase II post embryonic development cellular response to fibroblast growth factor stimulus renal vesicle morphogenesis lateral motor column neuron migration cerebellum development nervous system development transcription DNA templated nephric duct elongation ventral spinal cord development cervix development uterus development positive regulation of transcription DNA templated epithelium development mesonephros development multicellular organism development metanephric comma shaped body morphogenesis telencephalon development branching involved in ureteric bud morphogenesis forebrain regionalization positive regulation of anterior head development metanephric part of ureteric bud development S shaped body morphogenesis retina development in camera type eye nephric duct morphogenesis oviduct development spinal cord development embryonic retina morphogenesis in camera type eye animal organ morphogenesis regulation of gene expression paramesonephric duct development urogenital system development embryonic viscerocranium morphogenesis metanephric S shaped body morphogenesis endoderm formation anterior posterior axis specification horizontal cell localization positive regulation of embryonic development motor neuron axon guidance dorsal ventral pattern formation negative regulation of transcription DNA templated metanephros development primitive streak formation ectoderm formation anterior posterior pattern specification positive regulation of nephron tubule epithelial cell differentiation dorsal spinal cord interneuron posterior axon guidance regulation of transcription by RNA polymerase II neuron differentiation positive regulation of transcription by RNA polymerase II ureter morphogenesis endoderm development mesendoderm developmentSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez397516869EnsemblENSG00000273706ENSG00000274577ENSMUSG00000018698UniProtP48742Q58F18P63006RefSeq mRNA NM 005568NM 008498RefSeq protein NP 005559NP 005559 2NP 032524Location UCSC Chr 17 36 94 36 94 MbChr 11 84 41 84 42 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseFunction EditThe Lim gene family is a subfamily of homeobox genes 7 The homeobox genes are essential in organizing the body plan of an organism and all contain the same conserved homeodomain of amino acids 8 Evidence that Lim 1 is essential to a developing organism is its conservation throughout evolution and presence in a variety of organisms 7 The Lim 1 gene encodes a transcription factor which binds to the DNA of specific genes and functions to produce the needed gene product for development of the organism 9 Lim 1 is important during early molecular development and is required in both primitive streak derived tissue and visceral endoderm of the early embryo for development of a head 10 Studies done using mutant organisms without the Lim gene results in organisms that develop no head structure at all support the essential role of the Lim 1 gene in formation of the head 11 This gene has also been shown to play a crucial role in the formation of the female reproductive tract 9 The gene is expressed in the developing Mullerian duct of females and when the gene is knocked out no reproductive tract forms 9 Recent studies have shown that Lim 1 mutations may be one cause of the Mayer Rokitansky Kuster Hauser MRKH syndrome 12 MRKH is characterized by defective development or absence of the uterus and upper part of the vagina in women with normal ovaries and karyotype 12 Lim 1 s expression is controlled in part by the sonic hedgehog Gli signaling pathway 6 Recent studies in mice have shown that Lim 1 silencing halts tumor growth and impairs tumor cell movement via inhibition of protein expression involved in metastatic spread 6 Therefore in tumor cells Lim 1 acts as an oncogene 6 Thus targeting Lim 1 can be a potential cancer therapy In addition Lim 1 is important in rodent renal development 13 Lim 1 deficiency results in development of multicystic kidney whereas its expression can contribute to pathogenesis of nephroblastomas 13 Also Lim 1 plays a role in embryonic retinal development 14 Lim 1 expression affects differentiation and maintenance of horizontal cells located in the retinal thus it could serve as a marker in studies of horizontal cell specification 14 Lim 1 Lhx1 functions as a transcription factor necessary for regulating the production of coupling factors required for proper communication between the neurons located in the part of the brain responsible for regulation of circadian rhythms called the suprachiasmatic nucleus SCN 15 In mouse studies where Lim 1 transcription was restricted at some point during development in utero the individual units within the subject s molecular clock functioned properly but were unable to work together 15 Communication of these units is required to match their release of clock proteins which begin a transcription cascade of many other proteins that produce functional responses in tissues 15 The cyclic pattern of these responses is due to the feedback of the clock proteins and consequent changes to this transcription cascade 15 Reduced Lim 1 expression leads to inadequate levels of proteins such as Vasoactive Intestinal Polypeptide VIP that work to produce the neuron coordination required for a regulated circadian rhythm 15 The lack of such coupling factors causes the circadian clock to not function properly because the units within the SCN cannot match their release of clock proteins and therefore their transcriptional cascades of proteins that cause changes in arousal do not align 15 References Edit a b c ENSG00000274577 GRCh38 Ensembl release 89 ENSG00000273706 ENSG00000274577 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000018698 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene LHX1 LIM homeobox 1 a b c d Dormoy V et al 2011 LIM class homeobox gene Lim1 a novel oncogene in human renal cell carcinoma Oncogene 30 15 1753 1763 doi 10 1038 onc 2010 557 PMID 21132009 a b Hobert Oliver Heiner Westphal February 2000 Functions of LIM homeobox genes Trends in Genetics 16 2 75 83 doi 10 1016 S0168 9525 99 01883 1 PMID 10652534 Carlson BM 2009 Human Embryology and Developmental Biology Philadelphia PA Mosby Elsevier pp 67 70 ISBN 978 0 323 05385 3 a b c Kobayashi A Shawlot W Kania A Behringer RR Feb 2004 Requirement of Lim1 for female reproductive tract development Development 131 3 539 49 doi 10 1242 dev 00951 PMID 14695376 Shawlot W Wakamiya M Kwan KM Kania A Jessell TM Behringer RR Nov 1999 Lim1 is required in both primitive streak derived tissues and visceral endoderm for head formation in the mouse Development 126 22 4925 32 doi 10 1242 dev 126 22 4925 PMID 10529411 Bally Cuif L Boncinelli E Feb 1997 Transcription factors and head formation in vertebrates BioEssays 19 2 127 35 doi 10 1002 bies 950190207 PMID 9046242 S2CID 44679684 a b Ledig S Brucker S Barresi G Schomburg J Rall K Wieacker P Sep 2012 Frame shift mutation of LHX1 is associated with Mayer Rokitansky Kuster Hauser MRKH syndrome Human Reproduction 27 9 2872 5 doi 10 1093 humrep des206 PMID 22740494 a b Guertl B Senanayake U Nusshold E Leuschner I Mannweiler S Ebner B Hoefler G 2011 Lim1 an embryonal transcription factor is absent in multicystic renal dysplasia but reactivated in nephroblastomas Pathobiology 78 4 210 9 doi 10 1159 000326769 PMID 21778788 a b Liu W Wang JH Xiang M Mar 2000 Specific expression of the LIM homeodomain protein Lim 1 in horizontal cells during retinogenesis Developmental Dynamics 217 3 320 5 doi 10 1002 SICI 1097 0177 200003 217 3 lt 320 AID DVDY10 gt 3 0 CO 2 F PMID 10741426 a b c d e f Hatori M Gill S Mure LS Goulding M O Leary DD Panda S Jul 2014 Lhx1 maintains synchrony among circadian oscillator neurons of the SCN eLife 3 e03357 doi 10 7554 eLife 03357 PMC 4137275 PMID 25035422 Further reading EditShawlot W Behringer RR Mar 1995 Requirement for Lim1 in head organizer function Nature 374 6521 425 30 doi 10 1038 374425a0 PMID 7700351 S2CID 4353647 Bozzi F Bertuzzi S Strina D Giannetto C Vezzoni P Villa A Dec 1996 The exon intron structure of human LHX1 gene Biochemical and Biophysical Research Communications 229 2 494 7 doi 10 1006 bbrc 1996 1832 PMID 8954926 Dong WF Heng HH Lowsky R Xu Y DeCoteau JF Shi XM Tsui LC Minden MD Jun 1997 Cloning expression and chromosomal localization to 11p12 13 of a human LIM HOMEOBOX gene hLim 1 DNA and Cell Biology 16 6 671 8 doi 10 1089 dna 1997 16 671 hdl 10722 44331 PMID 9212161 Jurata LW Pfaff SL Gill GN Feb 1998 The nuclear LIM domain interactor NLI mediates homo and heterodimerization of LIM domain transcription factors The Journal of Biological Chemistry 273 6 3152 7 doi 10 1074 jbc 273 6 3152 PMID 9452425 Ostendorff HP Peirano RI Peters MA Schluter A Bossenz M Scheffner M Bach I Mar 2002 Ubiquitination dependent cofactor exchange on LIM homeodomain transcription factors Nature 416 6876 99 103 doi 10 1038 416099a PMID 11882901 S2CID 4426785 Phillips JC 2003 Assignment of LHX1 to human chromosome bands 17q11 2 gt q12 by use of radiation hybrid mapping and somatic cell hybridization Cytogenetic and Genome Research 97 1 2 140D doi 10 1159 000064048 PMID 12438757 Retrieved from https en wikipedia org w index php title LHX1 amp oldid 1109708785, wikipedia, wiki, book, books, library,
