Cargando…

The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin

O-acetyl-ADP-ribose (AAR) is a metabolic small molecule relevant in epigenetics that is generated by NAD-dependent histone deacetylases, such as Sir2. The formation of silent heterochromatin in yeast requires histone deacetylation by Sir2, structural rearrangement of SIR complexes, spreading of SIR...

Descripción completa

Detalles Bibliográficos
Autores principales: Tung, Shu-Yun, Wang, Sue-Hong, Lee, Sue-Ping, Tsai, Shu-Ping, Su, Kuan-Chung, Shen, Hsiao-Hsuian, Hong, Jia-Yang, Tsai, Ming-Shiun, Liou, Gunn-Guang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723988/
https://www.ncbi.nlm.nih.gov/pubmed/31366171
http://dx.doi.org/10.3390/genes10080577
_version_ 1783448899053158400
author Tung, Shu-Yun
Wang, Sue-Hong
Lee, Sue-Ping
Tsai, Shu-Ping
Su, Kuan-Chung
Shen, Hsiao-Hsuian
Hong, Jia-Yang
Tsai, Ming-Shiun
Liou, Gunn-Guang
author_facet Tung, Shu-Yun
Wang, Sue-Hong
Lee, Sue-Ping
Tsai, Shu-Ping
Su, Kuan-Chung
Shen, Hsiao-Hsuian
Hong, Jia-Yang
Tsai, Ming-Shiun
Liou, Gunn-Guang
author_sort Tung, Shu-Yun
collection PubMed
description O-acetyl-ADP-ribose (AAR) is a metabolic small molecule relevant in epigenetics that is generated by NAD-dependent histone deacetylases, such as Sir2. The formation of silent heterochromatin in yeast requires histone deacetylation by Sir2, structural rearrangement of SIR complexes, spreading of SIR complexes along the chromatin, and additional maturation processing. AAR affects the interactions of the SIR-nucleosome in vitro and enhances the chromatin epigenetic silencing effect in vivo. In this study, using isothermal titration calorimetry (ITC) and dot blotting methods, we showed the direct interaction of AAR with Sir3. Furthermore, through chromatin immunoprecipitation (ChIP)-on-chip and chromatin affinity purification (ChAP)-on chip assays, we discovered that AAR is capable of increasing the extended spreading of Sir3 along telomeres, but not Sir2. In addition, the findings of a quantitative real-time polymerase chain reaction (qRT-PCR) and examinations of an in vitro assembly system of SIR-nucleosome heterochromatin filament were consistent with these results. This study provides evidence indicating another important effect of AAR in vivo. AAR may play a specific modulating role in the formation of silent SIR-nucleosome heterochromatin in yeast.
format Online
Article
Text
id pubmed-6723988
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-67239882019-09-10 The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin Tung, Shu-Yun Wang, Sue-Hong Lee, Sue-Ping Tsai, Shu-Ping Su, Kuan-Chung Shen, Hsiao-Hsuian Hong, Jia-Yang Tsai, Ming-Shiun Liou, Gunn-Guang Genes (Basel) Article O-acetyl-ADP-ribose (AAR) is a metabolic small molecule relevant in epigenetics that is generated by NAD-dependent histone deacetylases, such as Sir2. The formation of silent heterochromatin in yeast requires histone deacetylation by Sir2, structural rearrangement of SIR complexes, spreading of SIR complexes along the chromatin, and additional maturation processing. AAR affects the interactions of the SIR-nucleosome in vitro and enhances the chromatin epigenetic silencing effect in vivo. In this study, using isothermal titration calorimetry (ITC) and dot blotting methods, we showed the direct interaction of AAR with Sir3. Furthermore, through chromatin immunoprecipitation (ChIP)-on-chip and chromatin affinity purification (ChAP)-on chip assays, we discovered that AAR is capable of increasing the extended spreading of Sir3 along telomeres, but not Sir2. In addition, the findings of a quantitative real-time polymerase chain reaction (qRT-PCR) and examinations of an in vitro assembly system of SIR-nucleosome heterochromatin filament were consistent with these results. This study provides evidence indicating another important effect of AAR in vivo. AAR may play a specific modulating role in the formation of silent SIR-nucleosome heterochromatin in yeast. MDPI 2019-07-30 /pmc/articles/PMC6723988/ /pubmed/31366171 http://dx.doi.org/10.3390/genes10080577 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tung, Shu-Yun
Wang, Sue-Hong
Lee, Sue-Ping
Tsai, Shu-Ping
Su, Kuan-Chung
Shen, Hsiao-Hsuian
Hong, Jia-Yang
Tsai, Ming-Shiun
Liou, Gunn-Guang
The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin
title The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin
title_full The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin
title_fullStr The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin
title_full_unstemmed The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin
title_short The Capability of O-Acetyl-ADP-Ribose, an Epigenetic Metabolic Small Molecule, on Promoting the Further Spreading of Sir3 along the Telomeric Chromatin
title_sort capability of o-acetyl-adp-ribose, an epigenetic metabolic small molecule, on promoting the further spreading of sir3 along the telomeric chromatin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723988/
https://www.ncbi.nlm.nih.gov/pubmed/31366171
http://dx.doi.org/10.3390/genes10080577
work_keys_str_mv AT tungshuyun thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT wangsuehong thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT leesueping thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT tsaishuping thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT sukuanchung thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT shenhsiaohsuian thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT hongjiayang thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT tsaimingshiun thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT liougunnguang thecapabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT tungshuyun capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT wangsuehong capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT leesueping capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT tsaishuping capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT sukuanchung capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT shenhsiaohsuian capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT hongjiayang capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT tsaimingshiun capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin
AT liougunnguang capabilityofoacetyladpriboseanepigeneticmetabolicsmallmoleculeonpromotingthefurtherspreadingofsir3alongthetelomericchromatin