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 |
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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 |
format | Article |
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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><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 & 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 & 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 ; Saijoh, Yukio ; Sakuma, Rui ; Tada, Masatomo ; Tomita, Naohiro ; Amano, Kenji ; Matsuda, Youichi ; Monden, Morito ; Okada, Shintaro ; Hamada, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5119-9e5e0bd44aa1a816f911678f779821ef2cee3f4f92dcfefb14190511379bf8293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Evolution, Molecular</topic><topic>Genetic Variation</topic><topic>Humans</topic><topic>Left-Right Determination Factors</topic><topic>LEFTY1 gene</topic><topic>LEFTY2 gene</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Phylogeny</topic><topic>Sequence Alignment</topic><topic>Transcription, Genetic</topic><topic>Transforming Growth Factor beta - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Genes to cells : devoted to molecular & cellular mechanisms</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yashiro, Kenta</au><au>Saijoh, Yukio</au><au>Sakuma, Rui</au><au>Tada, Masatomo</au><au>Tomita, Naohiro</au><au>Amano, Kenji</au><au>Matsuda, Youichi</au><au>Monden, Morito</au><au>Okada, Shintaro</au><au>Hamada, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes</atitle><jtitle>Genes to cells : devoted to molecular & cellular mechanisms</jtitle><addtitle>Genes Cells</addtitle><date>2000-05</date><risdate>2000</risdate><volume>5</volume><issue>5</issue><spage>343</spage><epage>357</epage><pages>343-357</pages><issn>1356-9597</issn><eissn>1365-2443</eissn><abstract>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.</abstract><cop>Oxford BSL</cop><pub>Blackwell Science Ltd</pub><pmid>10886363</pmid><doi>10.1046/j.1365-2443.2000.00329.x</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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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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