Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes
Abstract Arginine and lysine, frequently appearing as a pair on histones, have been proven to carry diverse modifications and execute various epigenetic regulatory functions. However, the most context‐specific and transient effectors of these marks, while significant, have evaded study as detection...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-04-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202307526 |
| _version_ | 1797215282890014720 |
|---|---|
| author | Yu Zong Nicole Weiss Ke Wang Alexandra E. Pagano Søren Heissel Sumera Perveen Jian Huang |
| author_facet | Yu Zong Nicole Weiss Ke Wang Alexandra E. Pagano Søren Heissel Sumera Perveen Jian Huang |
| author_sort | Yu Zong |
| collection | DOAJ |
| description | Abstract Arginine and lysine, frequently appearing as a pair on histones, have been proven to carry diverse modifications and execute various epigenetic regulatory functions. However, the most context‐specific and transient effectors of these marks, while significant, have evaded study as detection methods have thus far not reached a standard to capture these ephemeral events. Herein, a pair of complementary photo‐arginine/δ‐photo‐lysine (R‐dz/K‐dz) probes is developed and involve these into histone peptide, nucleosome, and chromatin substrates to capture and explore the interactomes of Arg and Lys hPTMs. By means of these developed tools, this study identifies that H3R2me2a can recruit MutS protein homolog 6 (MSH6), otherwise repelDouble PHD fingers 2 (DPF2), Retinoblastoma binding protein 4/7 (RBBP4/7). And it is disclosed that H3R2me2a inhibits the chromatin remodeling activity of the cBAF complex by blocking the interaction between DPF2 (one component of cBAF) and the nucleosome. In addition, the novel pairs of H4K5 PTMs and respective readers are highlighted, namely H4K5me‐Lethal(3)malignant brain tumor‐like protein 2 (L3MBTL2), H4K5me2‐L3MBTL2, and H4K5acK8ac‐YEATS domain‐containing protein 4 (YEATS4). These powerful tools pave the way for future investigation of related epigenetic mechanisms including but not limited to hPTMs. |
| first_indexed | 2024-04-24T11:27:36Z |
| format | Article |
| id | doaj.art-47298e61d3d842fd905d0b4d5040fd49 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-24T11:27:36Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-47298e61d3d842fd905d0b4d5040fd492024-04-10T13:10:11ZengWileyAdvanced Science2198-38442024-04-011114n/an/a10.1002/advs.202307526Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs InteractomesYu Zong0Nicole Weiss1Ke Wang2Alexandra E. Pagano3Søren Heissel4Sumera Perveen5Jian Huang6Chemical Biology Program Memorial Sloan Kettering Cancer Center New York 10065 USAProgram of Pharmacology Weill Cornell Medical College of Cornell University New York 10065 USAChemical Biology Program Memorial Sloan Kettering Cancer Center New York 10065 USAProteomics Resource Center Rockefeller University New York 10065 USAProteomics Resource Center Rockefeller University New York 10065 USAStructural Genomics Consortium University of Toronto Toronto M5S3H2 CanadaDepartment of Molecular Biology Princeton University Princeton 08544 USAAbstract Arginine and lysine, frequently appearing as a pair on histones, have been proven to carry diverse modifications and execute various epigenetic regulatory functions. However, the most context‐specific and transient effectors of these marks, while significant, have evaded study as detection methods have thus far not reached a standard to capture these ephemeral events. Herein, a pair of complementary photo‐arginine/δ‐photo‐lysine (R‐dz/K‐dz) probes is developed and involve these into histone peptide, nucleosome, and chromatin substrates to capture and explore the interactomes of Arg and Lys hPTMs. By means of these developed tools, this study identifies that H3R2me2a can recruit MutS protein homolog 6 (MSH6), otherwise repelDouble PHD fingers 2 (DPF2), Retinoblastoma binding protein 4/7 (RBBP4/7). And it is disclosed that H3R2me2a inhibits the chromatin remodeling activity of the cBAF complex by blocking the interaction between DPF2 (one component of cBAF) and the nucleosome. In addition, the novel pairs of H4K5 PTMs and respective readers are highlighted, namely H4K5me‐Lethal(3)malignant brain tumor‐like protein 2 (L3MBTL2), H4K5me2‐L3MBTL2, and H4K5acK8ac‐YEATS domain‐containing protein 4 (YEATS4). These powerful tools pave the way for future investigation of related epigenetic mechanisms including but not limited to hPTMs.https://doi.org/10.1002/advs.202307526nucleosome chromatin remodelingphoto‐argininepost‐translational modificationδ‐photo‐lysine |
| spellingShingle | Yu Zong Nicole Weiss Ke Wang Alexandra E. Pagano Søren Heissel Sumera Perveen Jian Huang Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes Advanced Science nucleosome chromatin remodeling photo‐arginine post‐translational modification δ‐photo‐lysine |
| title | Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes |
| title_full | Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes |
| title_fullStr | Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes |
| title_full_unstemmed | Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes |
| title_short | Development of Complementary Photo‐arginine/lysine to Promote Discovery of Arg/Lys hPTMs Interactomes |
| title_sort | development of complementary photo arginine lysine to promote discovery of arg lys hptms interactomes |
| topic | nucleosome chromatin remodeling photo‐arginine post‐translational modification δ‐photo‐lysine |
| url | https://doi.org/10.1002/advs.202307526 |
| work_keys_str_mv | AT yuzong developmentofcomplementaryphotoargininelysinetopromotediscoveryofarglyshptmsinteractomes AT nicoleweiss developmentofcomplementaryphotoargininelysinetopromotediscoveryofarglyshptmsinteractomes AT kewang developmentofcomplementaryphotoargininelysinetopromotediscoveryofarglyshptmsinteractomes AT alexandraepagano developmentofcomplementaryphotoargininelysinetopromotediscoveryofarglyshptmsinteractomes AT sørenheissel developmentofcomplementaryphotoargininelysinetopromotediscoveryofarglyshptmsinteractomes AT sumeraperveen developmentofcomplementaryphotoargininelysinetopromotediscoveryofarglyshptmsinteractomes AT jianhuang developmentofcomplementaryphotoargininelysinetopromotediscoveryofarglyshptmsinteractomes |