OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development
TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that mo...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/34870 |
| _version_ | 1811202726504169472 |
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| author | Joel Hrit Leeanne Goodrich Cheng Li Bang-An Wang Ji Nie Xiaolong Cui Elizabeth Allene Martin Eric Simental Jenna Fernandez Monica Yun Liu Joseph R Nery Rosa Castanon Rahul M Kohli Natalia Tretyakova Chuan He Joseph R Ecker Mary Goll Barbara Panning |
| author_facet | Joel Hrit Leeanne Goodrich Cheng Li Bang-An Wang Ji Nie Xiaolong Cui Elizabeth Allene Martin Eric Simental Jenna Fernandez Monica Yun Liu Joseph R Nery Rosa Castanon Rahul M Kohli Natalia Tretyakova Chuan He Joseph R Ecker Mary Goll Barbara Panning |
| author_sort | Joel Hrit |
| collection | DOAJ |
| description | TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a TET1 domain that is necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that this interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET2 and 5-methylcytosine, which is accompanied by alterations in gene expression. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes. |
| first_indexed | 2024-04-12T02:43:11Z |
| format | Article |
| id | doaj.art-a02f6ba8c3d5438d937c2000b1fe0c50 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:43:11Z |
| publishDate | 2018-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a02f6ba8c3d5438d937c2000b1fe0c502022-12-22T03:51:15ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.34870OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in developmentJoel Hrit0https://orcid.org/0000-0002-4497-956XLeeanne Goodrich1https://orcid.org/0000-0003-0603-4503Cheng Li2Bang-An Wang3https://orcid.org/0000-0003-4488-1738Ji Nie4Xiaolong Cui5Elizabeth Allene Martin6Eric Simental7https://orcid.org/0000-0002-8638-6578Jenna Fernandez8Monica Yun Liu9https://orcid.org/0000-0003-3936-9377Joseph R Nery10Rosa Castanon11Rahul M Kohli12Natalia Tretyakova13https://orcid.org/0000-0002-0621-6860Chuan He14https://orcid.org/0000-0003-4319-7424Joseph R Ecker15https://orcid.org/0000-0001-5799-5895Mary Goll16https://orcid.org/0000-0001-5003-6958Barbara Panning17https://orcid.org/0000-0002-8301-1172Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, United States; TETRAD Graduate Program, University of California San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, United States; TETRAD Graduate Program, University of California San Francisco, San Francisco, United StatesDevelopmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States; Program in Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology (BCMB Allied program), Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, United StatesGenomic Analysis Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesDepartment of Chemistry, Howard Hughes Medical Institute, University of Chicago, Chicago, United States; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States; Institute for Biophysical Dynamics, University of Chicago, Chicago, United StatesDepartment of Chemistry, Howard Hughes Medical Institute, University of Chicago, Chicago, United States; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States; Institute for Biophysical Dynamics, University of Chicago, Chicago, United StatesDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, United States; TETRAD Graduate Program, University of California San Francisco, San Francisco, United StatesDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, United States; TETRAD Graduate Program, University of California San Francisco, San Francisco, United StatesDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, United StatesDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesGenomic Analysis Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesGenomic Analysis Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Medicinal Chemistry, University of Minnesota, Minneapolis, United StatesDepartment of Chemistry, Howard Hughes Medical Institute, University of Chicago, Chicago, United States; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States; Institute for Biophysical Dynamics, University of Chicago, Chicago, United StatesGenomic Analysis Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United StatesDevelopmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, United StatesTET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a TET1 domain that is necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that this interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET2 and 5-methylcytosine, which is accompanied by alterations in gene expression. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.https://elifesciences.org/articles/34870TETOGTepigeneticschromatinstem cellsdevelopment |
| spellingShingle | Joel Hrit Leeanne Goodrich Cheng Li Bang-An Wang Ji Nie Xiaolong Cui Elizabeth Allene Martin Eric Simental Jenna Fernandez Monica Yun Liu Joseph R Nery Rosa Castanon Rahul M Kohli Natalia Tretyakova Chuan He Joseph R Ecker Mary Goll Barbara Panning OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development eLife TET OGT epigenetics chromatin stem cells development |
| title | OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development |
| title_full | OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development |
| title_fullStr | OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development |
| title_full_unstemmed | OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development |
| title_short | OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development |
| title_sort | ogt binds a conserved c terminal domain of tet1 to regulate tet1 activity and function in development |
| topic | TET OGT epigenetics chromatin stem cells development |
| url | https://elifesciences.org/articles/34870 |
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