Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases
Histone deacetylase 3 (HDAC3) and nuclear receptor co-repressor (NCoR1/2) are epigenetic regulators that play a key role in gene expression and metabolism. HDAC3 is a class I histone deacetylase that functions as a transcriptional co-repressor, modulating gene expression by removing acetyl groups fr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1190094/full |
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| author | Harikrishnareddy Paluvai Harikrishnareddy Paluvai Kumar D. Shanmukha Kumar D. Shanmukha Jens Tyedmers Jens Tyedmers Johannes Backs Johannes Backs |
| author_facet | Harikrishnareddy Paluvai Harikrishnareddy Paluvai Kumar D. Shanmukha Kumar D. Shanmukha Jens Tyedmers Jens Tyedmers Johannes Backs Johannes Backs |
| author_sort | Harikrishnareddy Paluvai |
| collection | DOAJ |
| description | Histone deacetylase 3 (HDAC3) and nuclear receptor co-repressor (NCoR1/2) are epigenetic regulators that play a key role in gene expression and metabolism. HDAC3 is a class I histone deacetylase that functions as a transcriptional co-repressor, modulating gene expression by removing acetyl groups from histones and non-histone proteins. NCoR1, on the other hand, is a transcriptional co-repressor that interacts with nuclear hormone receptors, including peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor (LXR), to regulate metabolic gene expression. Recent research has revealed a functional link between HDAC3 and NCoR1 in the regulation of metabolic gene expression. Genetic deletion of HDAC3 in mouse models has been shown to improve glucose intolerance and insulin sensitivity in the liver, skeletal muscle, and adipose tissue. Similarly, genetic deletion of NCoR1 has improved insulin resistance and reduced adiposity in mouse models. Dysregulation of this interaction has been associated with the development of cardio-metabolic diseases such as cardiovascular diseases, obesity and type 2 diabetes, suggesting that targeting this pathway may hold promise for the development of novel therapeutic interventions. In this review, we summarize the current understanding of individual functions of HDAC3 and NCoR1/2 and the co-repressor complex formation (HDAC3/NCoR1/2) in different metabolic tissues. Further studies are needed to thoroughly understand the mechanisms through which HDAC3, and NCoR1/2 govern metabolic processes and the implications for treating metabolic diseases. |
| first_indexed | 2024-03-12T13:58:35Z |
| format | Article |
| id | doaj.art-326bb1f37528494c8700580aed27bfaf |
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| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-12T13:58:35Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-326bb1f37528494c8700580aed27bfaf2023-08-22T10:24:02ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-08-011010.3389/fmolb.2023.11900941190094Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseasesHarikrishnareddy Paluvai0Harikrishnareddy Paluvai1Kumar D. Shanmukha2Kumar D. Shanmukha3Jens Tyedmers4Jens Tyedmers5Johannes Backs6Johannes Backs7Institute of Experimental Cardiology, Heidelberg University, Heidelberg, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyInstitute of Experimental Cardiology, Heidelberg University, Heidelberg, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyInstitute of Experimental Cardiology, Heidelberg University, Heidelberg, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyInstitute of Experimental Cardiology, Heidelberg University, Heidelberg, GermanyDZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyHistone deacetylase 3 (HDAC3) and nuclear receptor co-repressor (NCoR1/2) are epigenetic regulators that play a key role in gene expression and metabolism. HDAC3 is a class I histone deacetylase that functions as a transcriptional co-repressor, modulating gene expression by removing acetyl groups from histones and non-histone proteins. NCoR1, on the other hand, is a transcriptional co-repressor that interacts with nuclear hormone receptors, including peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor (LXR), to regulate metabolic gene expression. Recent research has revealed a functional link between HDAC3 and NCoR1 in the regulation of metabolic gene expression. Genetic deletion of HDAC3 in mouse models has been shown to improve glucose intolerance and insulin sensitivity in the liver, skeletal muscle, and adipose tissue. Similarly, genetic deletion of NCoR1 has improved insulin resistance and reduced adiposity in mouse models. Dysregulation of this interaction has been associated with the development of cardio-metabolic diseases such as cardiovascular diseases, obesity and type 2 diabetes, suggesting that targeting this pathway may hold promise for the development of novel therapeutic interventions. In this review, we summarize the current understanding of individual functions of HDAC3 and NCoR1/2 and the co-repressor complex formation (HDAC3/NCoR1/2) in different metabolic tissues. Further studies are needed to thoroughly understand the mechanisms through which HDAC3, and NCoR1/2 govern metabolic processes and the implications for treating metabolic diseases.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1190094/fullHDAC3NCoR1SMRTGPS2PPARs |
| spellingShingle | Harikrishnareddy Paluvai Harikrishnareddy Paluvai Kumar D. Shanmukha Kumar D. Shanmukha Jens Tyedmers Jens Tyedmers Johannes Backs Johannes Backs Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases Frontiers in Molecular Biosciences HDAC3 NCoR1 SMRT GPS2 PPARs |
| title | Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases |
| title_full | Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases |
| title_fullStr | Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases |
| title_full_unstemmed | Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases |
| title_short | Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases |
| title_sort | insights into the function of hdac3 and ncor1 ncor2 co repressor complex in metabolic diseases |
| topic | HDAC3 NCoR1 SMRT GPS2 PPARs |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1190094/full |
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