Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes

Background Mouse lefty1 and lefty2 genes are expressed on the left side of developing embryos and are required for left‐right determination. Here we have studied expression and transcriptional regulatory mechanisms of human LEFTY genes. Results The human LEFTY locus comprises two functional genes (L...

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Veröffentlicht in:Genes to cells : devoted to molecular & cellular mechanisms 2000-05, Vol.5 (5), p.343-357
Hauptverfasser: Yashiro, Kenta, Saijoh, Yukio, Sakuma, Rui, Tada, Masatomo, Tomita, Naohiro, Amano, Kenji, Matsuda, Youichi, Monden, Morito, Okada, Shintaro, Hamada, Hiroshi
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container_end_page 357
container_issue 5
container_start_page 343
container_title Genes to cells : devoted to molecular & cellular mechanisms
container_volume 5
creator Yashiro, Kenta
Saijoh, Yukio
Sakuma, Rui
Tada, Masatomo
Tomita, Naohiro
Amano, Kenji
Matsuda, Youichi
Monden, Morito
Okada, Shintaro
Hamada, Hiroshi
description Background Mouse lefty1 and lefty2 genes are expressed on the left side of developing embryos and are required for left‐right determination. Here we have studied expression and transcriptional regulatory mechanisms of human LEFTY genes. Results The human LEFTY locus comprises two functional genes (LEFTY1 and LEFTY2) and a putative pseudogene. LEFTY1 is expressed in colon crypts. However, whereas LEFTY1 mRNA is present in basal cells of the crypts, LEFTY1 protein is localized in the apical region, suggesting that this secreted protein undergoes long‐range transport. Human LEFTY2 possesses a left side‐specific enhancer (ASE) like mouse lefty2; however, the LEFTY2 ASE shows markedly higher activity in the floor plate than does the lefty2 ASE. In contrast to mouse lefty1, which is expressed predominantly in the floor plate under the control of a right side‐specific silencer, human LEFTY1 is expressed mainly in left lateral plate mesoderm under the control of an ASE‐like left side‐specific enhancer. The presence of FAST‐binding sites in the LEFTY1 enhancer (and their absence in lefty1) contributes to the difference. Conclusion These observations suggest that humans and mice have acquired distinct strategies during evolution for determining the asymmetric expression of LEFTY and lefty genes.
doi_str_mv 10.1046/j.1365-2443.2000.00329.x
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Conclusion These observations suggest that humans and mice have acquired distinct strategies during evolution for determining the asymmetric expression of LEFTY and lefty genes.</description><identifier>ISSN: 1356-9597</identifier><identifier>EISSN: 1365-2443</identifier><identifier>DOI: 10.1046/j.1365-2443.2000.00329.x</identifier><identifier>PMID: 10886363</identifier><language>eng</language><publisher>Oxford BSL: Blackwell Science Ltd</publisher><subject>Amino Acid Sequence ; Animals ; Base Sequence ; Evolution, Molecular ; Genetic Variation ; Humans ; Left-Right Determination Factors ; LEFTY1 gene ; LEFTY2 gene ; Mice ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Transcription, Genetic ; Transforming Growth Factor beta - genetics</subject><ispartof>Genes to cells : devoted to molecular &amp; cellular mechanisms, 2000-05, Vol.5 (5), p.343-357</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5119-9e5e0bd44aa1a816f911678f779821ef2cee3f4f92dcfefb14190511379bf8293</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2443.2000.00329.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2443.2000.00329.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10886363$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yashiro, Kenta</creatorcontrib><creatorcontrib>Saijoh, Yukio</creatorcontrib><creatorcontrib>Sakuma, Rui</creatorcontrib><creatorcontrib>Tada, Masatomo</creatorcontrib><creatorcontrib>Tomita, Naohiro</creatorcontrib><creatorcontrib>Amano, Kenji</creatorcontrib><creatorcontrib>Matsuda, Youichi</creatorcontrib><creatorcontrib>Monden, Morito</creatorcontrib><creatorcontrib>Okada, Shintaro</creatorcontrib><creatorcontrib>Hamada, Hiroshi</creatorcontrib><title>Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes</title><title>Genes to cells : devoted to molecular &amp; cellular mechanisms</title><addtitle>Genes Cells</addtitle><description>Background Mouse lefty1 and lefty2 genes are expressed on the left side of developing embryos and are required for left‐right determination. Here we have studied expression and transcriptional regulatory mechanisms of human LEFTY genes. Results The human LEFTY locus comprises two functional genes (LEFTY1 and LEFTY2) and a putative pseudogene. LEFTY1 is expressed in colon crypts. However, whereas LEFTY1 mRNA is present in basal cells of the crypts, LEFTY1 protein is localized in the apical region, suggesting that this secreted protein undergoes long‐range transport. Human LEFTY2 possesses a left side‐specific enhancer (ASE) like mouse lefty2; however, the LEFTY2 ASE shows markedly higher activity in the floor plate than does the lefty2 ASE. In contrast to mouse lefty1, which is expressed predominantly in the floor plate under the control of a right side‐specific silencer, human LEFTY1 is expressed mainly in left lateral plate mesoderm under the control of an ASE‐like left side‐specific enhancer. The presence of FAST‐binding sites in the LEFTY1 enhancer (and their absence in lefty1) contributes to the difference. Conclusion These observations suggest that humans and mice have acquired distinct strategies during evolution for determining the asymmetric expression of LEFTY and lefty genes.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Evolution, Molecular</subject><subject>Genetic Variation</subject><subject>Humans</subject><subject>Left-Right Determination Factors</subject><subject>LEFTY1 gene</subject><subject>LEFTY2 gene</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Phylogeny</subject><subject>Sequence Alignment</subject><subject>Transcription, Genetic</subject><subject>Transforming Growth Factor beta - genetics</subject><issn>1356-9597</issn><issn>1365-2443</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1v2zAMhoVixdJ1-wuFTrvZE_VhW0AvQ9ZkBQL0kh12EhSZahQ4dibZa_LvZy9F0Vt7Igk-Lwk8hFBgOTBZfNvlIAqVcSlFzhljOWOC6_x4Qa5eFh-mXhWZVrqckU8p7RgDwZn6SGbAqqoQhbgi6x8h9aF1Pe2jbZOL4dCHrrUNjfg4NHYaqG1retiemu4RW-yDo3X4i3EcHNLO0-2wty1d3S3Wv-lEpM_k0tsm4Zfnek1-Le7W85_Z6mF5P_--ypwC0JlGhWxTS2kt2AoKrwGKsvJlqSsO6LlDFF56zWvn0W9AgmZjUpR64yuuxTX5er57iN2fAVNv9iE5bBrbYjckUwIvmQT1JgilUlKqagSrM-hil1JEbw4x7G08GWBmUm92ZjJsJsNmUm_-qzfHMXrz_GPY7LF-FTy7HoHbM_AUGjy9-7BZrudjI_4BXgOSPg</recordid><startdate>200005</startdate><enddate>200005</enddate><creator>Yashiro, Kenta</creator><creator>Saijoh, Yukio</creator><creator>Sakuma, Rui</creator><creator>Tada, Masatomo</creator><creator>Tomita, Naohiro</creator><creator>Amano, Kenji</creator><creator>Matsuda, Youichi</creator><creator>Monden, Morito</creator><creator>Okada, Shintaro</creator><creator>Hamada, Hiroshi</creator><general>Blackwell Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200005</creationdate><title>Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes</title><author>Yashiro, Kenta ; 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subjects Amino Acid Sequence
Animals
Base Sequence
Evolution, Molecular
Genetic Variation
Humans
Left-Right Determination Factors
LEFTY1 gene
LEFTY2 gene
Mice
Molecular Sequence Data
Phylogeny
Sequence Alignment
Transcription, Genetic
Transforming Growth Factor beta - genetics
title Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes
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