Real-Time Imaging of Histone H4K12–Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors
Histone acetylation constitutes an epigenetic mark for transcriptional regulation. Here we developed a fluorescent probe to visualize acetylation of histone H4 Lys12 (H4K12) in living cells using fluorescence resonance energy transfer (FRET) and the binding of the BRD2 bromodomain to acetylated H4K1...
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| Veröffentlicht in: | Chemistry & biology 2011-04, Vol.18 (4), p.495-507 |
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| creator | Ito, Tamaki Umehara, Takashi Sasaki, Kazuki Nakamura, Yoshihiro Nishino, Norikazu Terada, Takaho Shirouzu, Mikako Padmanabhan, Balasundaram Yokoyama, Shigeyuki Ito, Akihiro Yoshida, Minoru |
| description | Histone acetylation constitutes an epigenetic mark for transcriptional regulation. Here we developed a fluorescent probe to visualize acetylation of histone H4 Lys12 (H4K12) in living cells using fluorescence resonance energy transfer (FRET) and the binding of the BRD2 bromodomain to acetylated H4K12. Using this probe designated as Histac-K12, we demonstrated that histone H4K12 acetylation is retained in mitosis and that some histone deacetylase (HDAC) inhibitors continue to inhibit cellular HDAC activity even after their removal from the culture. In addition, a small molecule that interferes with ability of the bromodomain to bind to acetylated H4K12 could be assessed using Histac-K12 in cells. Thus, Histac-K12 will serve as a powerful tool not only to understand the dynamics of H4K12-specific acetylation but also to characterize small molecules that modulate the acetylation or interaction status of histones.
[Display omitted]
► Development of a FRET-based probe for visualizing histone H4K12 acetylation ► Real-time quantification of H4K12 acetylation dynamics during mitosis ► Description of H4K12 acetylation dynamics in living cells using HDAC inhibitors ► Identification of a compound that inhibits BRD2 association with H4K12 acetylation |
| doi_str_mv | 10.1016/j.chembiol.2011.02.009 |
| format | Article |
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[Display omitted]
► Development of a FRET-based probe for visualizing histone H4K12 acetylation ► Real-time quantification of H4K12 acetylation dynamics during mitosis ► Description of H4K12 acetylation dynamics in living cells using HDAC inhibitors ► Identification of a compound that inhibits BRD2 association with H4K12 acetylation</description><identifier>ISSN: 1074-5521</identifier><identifier>EISSN: 1879-1301</identifier><identifier>DOI: 10.1016/j.chembiol.2011.02.009</identifier><identifier>PMID: 21513886</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Acetylation - drug effects ; Animals ; Binding Sites ; Cell Survival ; Cercopithecus aethiops ; Chromosomes - drug effects ; Chromosomes - metabolism ; COS Cells ; Drug Design ; Fluorescent Dyes - metabolism ; Histone Deacetylase Inhibitors - pharmacology ; Histone Deacetylases - chemistry ; Histone Deacetylases - genetics ; Histone Deacetylases - metabolism ; Histones - chemistry ; Histones - metabolism ; Kinetics ; Lysine ; Mitosis - drug effects ; Models, Molecular ; Molecular Imaging ; Mutation ; Protein Structure, Tertiary - drug effects ; Substrate Specificity ; Time Factors ; Transcription, Genetic - drug effects</subject><ispartof>Chemistry & biology, 2011-04, Vol.18 (4), p.495-507</ispartof><rights>2011 Elsevier Ltd</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-f378d688966440a45e29fb2b4c8a7346723983419daad9eaad5af4ded5d4f2b63</citedby><cites>FETCH-LOGICAL-c433t-f378d688966440a45e29fb2b4c8a7346723983419daad9eaad5af4ded5d4f2b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1074552111000780$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21513886$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ito, Tamaki</creatorcontrib><creatorcontrib>Umehara, Takashi</creatorcontrib><creatorcontrib>Sasaki, Kazuki</creatorcontrib><creatorcontrib>Nakamura, Yoshihiro</creatorcontrib><creatorcontrib>Nishino, Norikazu</creatorcontrib><creatorcontrib>Terada, Takaho</creatorcontrib><creatorcontrib>Shirouzu, Mikako</creatorcontrib><creatorcontrib>Padmanabhan, Balasundaram</creatorcontrib><creatorcontrib>Yokoyama, Shigeyuki</creatorcontrib><creatorcontrib>Ito, Akihiro</creatorcontrib><creatorcontrib>Yoshida, Minoru</creatorcontrib><title>Real-Time Imaging of Histone H4K12–Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors</title><title>Chemistry & biology</title><addtitle>Chem Biol</addtitle><description>Histone acetylation constitutes an epigenetic mark for transcriptional regulation. Here we developed a fluorescent probe to visualize acetylation of histone H4 Lys12 (H4K12) in living cells using fluorescence resonance energy transfer (FRET) and the binding of the BRD2 bromodomain to acetylated H4K12. Using this probe designated as Histac-K12, we demonstrated that histone H4K12 acetylation is retained in mitosis and that some histone deacetylase (HDAC) inhibitors continue to inhibit cellular HDAC activity even after their removal from the culture. In addition, a small molecule that interferes with ability of the bromodomain to bind to acetylated H4K12 could be assessed using Histac-K12 in cells. Thus, Histac-K12 will serve as a powerful tool not only to understand the dynamics of H4K12-specific acetylation but also to characterize small molecules that modulate the acetylation or interaction status of histones.
[Display omitted]
► Development of a FRET-based probe for visualizing histone H4K12 acetylation ► Real-time quantification of H4K12 acetylation dynamics during mitosis ► Description of H4K12 acetylation dynamics in living cells using HDAC inhibitors ► Identification of a compound that inhibits BRD2 association with H4K12 acetylation</description><subject>Acetylation - drug effects</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Cell Survival</subject><subject>Cercopithecus aethiops</subject><subject>Chromosomes - drug effects</subject><subject>Chromosomes - metabolism</subject><subject>COS Cells</subject><subject>Drug Design</subject><subject>Fluorescent Dyes - metabolism</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylases - chemistry</subject><subject>Histone Deacetylases - genetics</subject><subject>Histone Deacetylases - metabolism</subject><subject>Histones - chemistry</subject><subject>Histones - metabolism</subject><subject>Kinetics</subject><subject>Lysine</subject><subject>Mitosis - drug effects</subject><subject>Models, Molecular</subject><subject>Molecular Imaging</subject><subject>Mutation</subject><subject>Protein Structure, Tertiary - drug effects</subject><subject>Substrate Specificity</subject><subject>Time Factors</subject><subject>Transcription, Genetic - drug effects</subject><issn>1074-5521</issn><issn>1879-1301</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAQjRAVLYW_UPnGKcFfcZwbS0u7K1ohQTlbjj3pehXbi52t1BvnXvsP-SW4bIu4cZl50rz3RjOvqk4Ibggm4v2mMWvwg4tTQzEhDaYNxv2L6ojIrq8Jw-RlwbjjddtScli9znmDMSayF6-qQ0pawqQUR9X9V9BTfe08oJXXNy7coDiipctzDICW_DOhv34-fNuCcaMzaGFgvpv07GJAZzBD8i5ARvMa0FW0BRXxwvwZ_2NzBnqvy4B0sOhjij7a6LULaBXWbnBzTPlNdTDqKcPbp35cfT__dH26rC-_XKxOF5e14YzN9cg6aYUshwjOseYt0H4c6MCN1B3joqOsl4yT3mpteyil1SO3YFvLRzoIdly92_tuU_yxgzwr77KBadIB4i4rKRhnuGekMMWeaVLMOcGotsl5ne4UweoxBrVRzzGoxxgUpqrEUIQnTyt2gwf7V_b890L4sCdAOfTWQVLZOAgGrEtgZmWj-9-O3_0Unoc</recordid><startdate>20110422</startdate><enddate>20110422</enddate><creator>Ito, Tamaki</creator><creator>Umehara, Takashi</creator><creator>Sasaki, Kazuki</creator><creator>Nakamura, Yoshihiro</creator><creator>Nishino, Norikazu</creator><creator>Terada, Takaho</creator><creator>Shirouzu, Mikako</creator><creator>Padmanabhan, Balasundaram</creator><creator>Yokoyama, Shigeyuki</creator><creator>Ito, Akihiro</creator><creator>Yoshida, Minoru</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope></search><sort><creationdate>20110422</creationdate><title>Real-Time Imaging of Histone H4K12–Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors</title><author>Ito, Tamaki ; Umehara, Takashi ; Sasaki, Kazuki ; Nakamura, Yoshihiro ; Nishino, Norikazu ; Terada, Takaho ; Shirouzu, Mikako ; Padmanabhan, Balasundaram ; Yokoyama, Shigeyuki ; Ito, Akihiro ; Yoshida, Minoru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-f378d688966440a45e29fb2b4c8a7346723983419daad9eaad5af4ded5d4f2b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acetylation - drug effects</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Cell Survival</topic><topic>Cercopithecus aethiops</topic><topic>Chromosomes - drug effects</topic><topic>Chromosomes - metabolism</topic><topic>COS Cells</topic><topic>Drug Design</topic><topic>Fluorescent Dyes - metabolism</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histone Deacetylases - chemistry</topic><topic>Histone Deacetylases - genetics</topic><topic>Histone Deacetylases - metabolism</topic><topic>Histones - chemistry</topic><topic>Histones - metabolism</topic><topic>Kinetics</topic><topic>Lysine</topic><topic>Mitosis - drug effects</topic><topic>Models, Molecular</topic><topic>Molecular Imaging</topic><topic>Mutation</topic><topic>Protein Structure, Tertiary - drug effects</topic><topic>Substrate Specificity</topic><topic>Time Factors</topic><topic>Transcription, Genetic - drug effects</topic><toplevel>online_resources</toplevel><creatorcontrib>Ito, Tamaki</creatorcontrib><creatorcontrib>Umehara, Takashi</creatorcontrib><creatorcontrib>Sasaki, Kazuki</creatorcontrib><creatorcontrib>Nakamura, Yoshihiro</creatorcontrib><creatorcontrib>Nishino, Norikazu</creatorcontrib><creatorcontrib>Terada, Takaho</creatorcontrib><creatorcontrib>Shirouzu, Mikako</creatorcontrib><creatorcontrib>Padmanabhan, Balasundaram</creatorcontrib><creatorcontrib>Yokoyama, Shigeyuki</creatorcontrib><creatorcontrib>Ito, Akihiro</creatorcontrib><creatorcontrib>Yoshida, Minoru</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry & biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ito, Tamaki</au><au>Umehara, Takashi</au><au>Sasaki, Kazuki</au><au>Nakamura, Yoshihiro</au><au>Nishino, Norikazu</au><au>Terada, Takaho</au><au>Shirouzu, Mikako</au><au>Padmanabhan, Balasundaram</au><au>Yokoyama, Shigeyuki</au><au>Ito, Akihiro</au><au>Yoshida, Minoru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Real-Time Imaging of Histone H4K12–Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors</atitle><jtitle>Chemistry & biology</jtitle><addtitle>Chem Biol</addtitle><date>2011-04-22</date><risdate>2011</risdate><volume>18</volume><issue>4</issue><spage>495</spage><epage>507</epage><pages>495-507</pages><issn>1074-5521</issn><eissn>1879-1301</eissn><abstract>Histone acetylation constitutes an epigenetic mark for transcriptional regulation. 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[Display omitted]
► Development of a FRET-based probe for visualizing histone H4K12 acetylation ► Real-time quantification of H4K12 acetylation dynamics during mitosis ► Description of H4K12 acetylation dynamics in living cells using HDAC inhibitors ► Identification of a compound that inhibits BRD2 association with H4K12 acetylation</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>21513886</pmid><doi>10.1016/j.chembiol.2011.02.009</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Chemistry & biology, 2011-04, Vol.18 (4), p.495-507 |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Acetylation - drug effects Animals Binding Sites Cell Survival Cercopithecus aethiops Chromosomes - drug effects Chromosomes - metabolism COS Cells Drug Design Fluorescent Dyes - metabolism Histone Deacetylase Inhibitors - pharmacology Histone Deacetylases - chemistry Histone Deacetylases - genetics Histone Deacetylases - metabolism Histones - chemistry Histones - metabolism Kinetics Lysine Mitosis - drug effects Models, Molecular Molecular Imaging Mutation Protein Structure, Tertiary - drug effects Substrate Specificity Time Factors Transcription, Genetic - drug effects |
| title | Real-Time Imaging of Histone H4K12–Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors |
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