Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription
We report the cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless (dtim) gene. The mammalian Tim genes are widely expressed in a variety of tissues; however, unlike Drosophila, mTim mRNA levels do not oscillate in the suprachiasmatic nucleus (SCN) or retina. Imp...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 1998-11, Vol.21 (5), p.1101-1113 |
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| creator | Sangoram, A M Saez, L Antoch, M P Gekakis, N Staknis, D Whiteley, A Fruechte, E M Vitaterna, M H Shimomura, K King, D P Young, M W Weitz, C J Takahashi, J S |
| description | We report the cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless (dtim) gene. The mammalian Tim genes are widely expressed in a variety of tissues; however, unlike Drosophila, mTim mRNA levels do not oscillate in the suprachiasmatic nucleus (SCN) or retina. Importantly, hTIM interacts with the Drosophila PERIOD (dPER) protein as well as the mouse PER1 and PER2 proteins in vitro. In Drosophila (S2) cells, hTIM and dPER interact and translocate into the nucleus. Finally, hTIM and mPER1 specifically inhibit CLOCK-BMAL1-induced transactivation of the mPer1 promoter. Taken together, these results demonstrate that mTim and hTIM are mammalian orthologs of timeless and provide a framework for a basic circadian autoregulatory loop in mammals. |
| doi_str_mv | 10.1016/S0896-6273(00)80627-3 |
| format | Article |
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The mammalian Tim genes are widely expressed in a variety of tissues; however, unlike Drosophila, mTim mRNA levels do not oscillate in the suprachiasmatic nucleus (SCN) or retina. Importantly, hTIM interacts with the Drosophila PERIOD (dPER) protein as well as the mouse PER1 and PER2 proteins in vitro. In Drosophila (S2) cells, hTIM and dPER interact and translocate into the nucleus. Finally, hTIM and mPER1 specifically inhibit CLOCK-BMAL1-induced transactivation of the mPer1 promoter. 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Taken together, these results demonstrate that mTim and hTIM are mammalian orthologs of timeless and provide a framework for a basic circadian autoregulatory loop in mammals.</description><subject>Alternative Splicing - genetics</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>ARNTL Transcription Factors</subject><subject>Basic Helix-Loop-Helix Transcription Factors</subject><subject>Biological Clocks - genetics</subject><subject>BMAL1 protein</subject><subject>cDNA</subject><subject>Cell Cycle Proteins</subject><subject>Cell Line</subject><subject>Chromosome Mapping</subject><subject>Chromosomes, Human, Pair 12 - genetics</subject><subject>Circadian Rhythm - genetics</subject><subject>CLOCK protein</subject><subject>CLOCK Proteins</subject><subject>Cloning, Molecular</subject><subject>Drosophila</subject><subject>Drosophila Proteins</subject><subject>Female</subject><subject>hTIM gene</subject><subject>Humans</subject><subject>Insect Proteins - genetics</subject><subject>Insect Proteins - metabolism</subject><subject>Insect Proteins - physiology</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Mammalia</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Sequence Data</subject><subject>mPer1 gene</subject><subject>mTim gene</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nuclear Proteins - physiology</subject><subject>Period Circadian Proteins</subject><subject>Polymorphism, Genetic</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Tim gene</subject><subject>Timeless (tim) gene</subject><subject>Trans-Activators - antagonists & inhibitors</subject><subject>Trans-Activators - genetics</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription Factors - physiology</subject><issn>0896-6273</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkL1OwzAcxD2ASik8QiVPCIaAHSdOzFYqvkSrItE9-td2ipETB9tB6iPw1gSoWJnudPrppDuEppRcUkL51QspBU94WrBzQi5KMriEHaDxX3yEjkN4I4RmuaAjNBJlzjOej9HnEpoGrIEWS-MlqG8HfXReb3sLg-6wda67xoCjabTVIWDn46uzbouhVbh51p5i00btQcafqNVbiOZD2x3e12g8X6zmT8nNcragiWlVL7XC0UMbpDddNK49QYc12KBP9zpB67vb9fwhWazuH-ezRdKlrIhJvqGM1SmoLK25BpbLclhZMNhktVCU1plgnEgGGUiqOBc1bFSdMp3lABzYBJ391nbevfc6xKoxQWprodWuDxUXpCxJVvwL0oKJkqViAKd7sN80WlWdNw34XbX_mH0BP91_wQ</recordid><startdate>19981101</startdate><enddate>19981101</enddate><creator>Sangoram, A M</creator><creator>Saez, L</creator><creator>Antoch, M P</creator><creator>Gekakis, N</creator><creator>Staknis, D</creator><creator>Whiteley, A</creator><creator>Fruechte, E M</creator><creator>Vitaterna, M H</creator><creator>Shimomura, K</creator><creator>King, D P</creator><creator>Young, M W</creator><creator>Weitz, C J</creator><creator>Takahashi, J S</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19981101</creationdate><title>Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription</title><author>Sangoram, A M ; Saez, L ; Antoch, M P ; Gekakis, N ; Staknis, D ; Whiteley, A ; Fruechte, E M ; Vitaterna, M H ; Shimomura, K ; King, D P ; Young, M W ; Weitz, C J ; Takahashi, J S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p237t-5b133f2ad42f6ea35c808973ab4f9d11f49360c3a4ac1d669fabdf23e45aa6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Alternative Splicing - genetics</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>ARNTL Transcription Factors</topic><topic>Basic Helix-Loop-Helix Transcription Factors</topic><topic>Biological Clocks - genetics</topic><topic>BMAL1 protein</topic><topic>cDNA</topic><topic>Cell Cycle Proteins</topic><topic>Cell Line</topic><topic>Chromosome Mapping</topic><topic>Chromosomes, Human, Pair 12 - genetics</topic><topic>Circadian Rhythm - genetics</topic><topic>CLOCK protein</topic><topic>CLOCK Proteins</topic><topic>Cloning, Molecular</topic><topic>Drosophila</topic><topic>Drosophila Proteins</topic><topic>Female</topic><topic>hTIM gene</topic><topic>Humans</topic><topic>Insect Proteins - genetics</topic><topic>Insect Proteins - metabolism</topic><topic>Insect Proteins - physiology</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Mammalia</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Sequence Data</topic><topic>mPer1 gene</topic><topic>mTim gene</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nuclear Proteins - physiology</topic><topic>Period Circadian Proteins</topic><topic>Polymorphism, Genetic</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Tim gene</topic><topic>Timeless (tim) gene</topic><topic>Trans-Activators - antagonists & inhibitors</topic><topic>Trans-Activators - genetics</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription Factors - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sangoram, A M</creatorcontrib><creatorcontrib>Saez, L</creatorcontrib><creatorcontrib>Antoch, M P</creatorcontrib><creatorcontrib>Gekakis, N</creatorcontrib><creatorcontrib>Staknis, D</creatorcontrib><creatorcontrib>Whiteley, A</creatorcontrib><creatorcontrib>Fruechte, E M</creatorcontrib><creatorcontrib>Vitaterna, M H</creatorcontrib><creatorcontrib>Shimomura, K</creatorcontrib><creatorcontrib>King, D P</creatorcontrib><creatorcontrib>Young, M W</creatorcontrib><creatorcontrib>Weitz, C J</creatorcontrib><creatorcontrib>Takahashi, J S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</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>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sangoram, A M</au><au>Saez, L</au><au>Antoch, M P</au><au>Gekakis, N</au><au>Staknis, D</au><au>Whiteley, A</au><au>Fruechte, E M</au><au>Vitaterna, M H</au><au>Shimomura, K</au><au>King, D P</au><au>Young, M W</au><au>Weitz, C J</au><au>Takahashi, J S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>1998-11-01</date><risdate>1998</risdate><volume>21</volume><issue>5</issue><spage>1101</spage><epage>1113</epage><pages>1101-1113</pages><issn>0896-6273</issn><abstract>We report the cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless (dtim) gene. The mammalian Tim genes are widely expressed in a variety of tissues; however, unlike Drosophila, mTim mRNA levels do not oscillate in the suprachiasmatic nucleus (SCN) or retina. Importantly, hTIM interacts with the Drosophila PERIOD (dPER) protein as well as the mouse PER1 and PER2 proteins in vitro. In Drosophila (S2) cells, hTIM and dPER interact and translocate into the nucleus. Finally, hTIM and mPER1 specifically inhibit CLOCK-BMAL1-induced transactivation of the mPer1 promoter. Taken together, these results demonstrate that mTim and hTIM are mammalian orthologs of timeless and provide a framework for a basic circadian autoregulatory loop in mammals.</abstract><cop>United States</cop><pmid>9856465</pmid><doi>10.1016/S0896-6273(00)80627-3</doi><tpages>13</tpages></addata></record> |
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| identifier | ISSN: 0896-6273 |
| ispartof | Neuron (Cambridge, Mass.), 1998-11, Vol.21 (5), p.1101-1113 |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | Alternative Splicing - genetics Amino Acid Sequence Animals ARNTL Transcription Factors Basic Helix-Loop-Helix Transcription Factors Biological Clocks - genetics BMAL1 protein cDNA Cell Cycle Proteins Cell Line Chromosome Mapping Chromosomes, Human, Pair 12 - genetics Circadian Rhythm - genetics CLOCK protein CLOCK Proteins Cloning, Molecular Drosophila Drosophila Proteins Female hTIM gene Humans Insect Proteins - genetics Insect Proteins - metabolism Insect Proteins - physiology Intracellular Signaling Peptides and Proteins Mammalia Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Molecular Sequence Data mPer1 gene mTim gene Nuclear Proteins - metabolism Nuclear Proteins - physiology Period Circadian Proteins Polymorphism, Genetic RNA, Messenger - biosynthesis Tim gene Timeless (tim) gene Trans-Activators - antagonists & inhibitors Trans-Activators - genetics Transcription Factors - genetics Transcription Factors - metabolism Transcription Factors - physiology |
| title | Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription |
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