Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes
PARP-1, also known as poly(ADP-ribose) polymerase 1, is a multifunctional nuclear enzyme that plays a critical role in transcriptional regulation through its three functional domains: the N-terminal DNA-binding domain (DBD) containing two zinc fingers for DNA binding and a third zinc finger for main...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1152570/full |
| _version_ | 1797810190809038848 |
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| author | Gbolahan Bamgbose Sarah Johnson Alexei Tulin |
| author_facet | Gbolahan Bamgbose Sarah Johnson Alexei Tulin |
| author_sort | Gbolahan Bamgbose |
| collection | DOAJ |
| description | PARP-1, also known as poly(ADP-ribose) polymerase 1, is a multifunctional nuclear enzyme that plays a critical role in transcriptional regulation through its three functional domains: the N-terminal DNA-binding domain (DBD) containing two zinc fingers for DNA binding and a third zinc finger for maintaining interdomain contacts, the auto modification domain (AD), and the C-terminal domain, which includes the protein-interacting WGR domain and the catalytic domain. Despite the critical role that PARP-1 plays in regulating gene expression, the mechanisms by which it is targeted to chromatin are not well understood. In this study, we aimed to understand the targeting of PARP-1 to chromatin using ChIP-seq of YFP-tagged deletional isoforms of PARP-1 (ZnI, ZnII, AD-WGR) and a construct that lacks only ZnI (ΔZnI). Our results indicate that other PARP-1 domains are sufficient to target PARP-1 to active genes in the absence of ZnI. Furthermore, we found that PARP-1 represses metabolic gene pathways and activates developmental gene pathways. The results of ChIP-seq analysis showed that PARP-1 and ΔZnI were preferentially bound to the gene bodies of PARP-1-regulated metabolic genes compared to developmental genes. PARP-1 domains (ZnI, ZnII and AD-WGR) also preferentially occupied the gene bodies of PARP-1-regulated metabolic genes, however, they were more enriched at the TSS of PARP-1-regulated developmental genes compared to metabolic genes. Thus, we propose that PARP-1 domains cooperatively target PARP-1 to PARP-1-regulated genes to coordinate metabolic and developmental gene expression programs. |
| first_indexed | 2024-03-13T07:04:32Z |
| format | Article |
| id | doaj.art-7d7b2522844544948811ae854cec4818 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-13T07:04:32Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-7d7b2522844544948811ae854cec48182023-06-06T12:57:33ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-06-011410.3389/fendo.2023.11525701152570Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genesGbolahan BamgboseSarah JohnsonAlexei TulinPARP-1, also known as poly(ADP-ribose) polymerase 1, is a multifunctional nuclear enzyme that plays a critical role in transcriptional regulation through its three functional domains: the N-terminal DNA-binding domain (DBD) containing two zinc fingers for DNA binding and a third zinc finger for maintaining interdomain contacts, the auto modification domain (AD), and the C-terminal domain, which includes the protein-interacting WGR domain and the catalytic domain. Despite the critical role that PARP-1 plays in regulating gene expression, the mechanisms by which it is targeted to chromatin are not well understood. In this study, we aimed to understand the targeting of PARP-1 to chromatin using ChIP-seq of YFP-tagged deletional isoforms of PARP-1 (ZnI, ZnII, AD-WGR) and a construct that lacks only ZnI (ΔZnI). Our results indicate that other PARP-1 domains are sufficient to target PARP-1 to active genes in the absence of ZnI. Furthermore, we found that PARP-1 represses metabolic gene pathways and activates developmental gene pathways. The results of ChIP-seq analysis showed that PARP-1 and ΔZnI were preferentially bound to the gene bodies of PARP-1-regulated metabolic genes compared to developmental genes. PARP-1 domains (ZnI, ZnII and AD-WGR) also preferentially occupied the gene bodies of PARP-1-regulated metabolic genes, however, they were more enriched at the TSS of PARP-1-regulated developmental genes compared to metabolic genes. Thus, we propose that PARP-1 domains cooperatively target PARP-1 to PARP-1-regulated genes to coordinate metabolic and developmental gene expression programs.https://www.frontiersin.org/articles/10.3389/fendo.2023.1152570/fullPARP-1metabolic genesdevelopmental genesgene expressionPARP-1 domains |
| spellingShingle | Gbolahan Bamgbose Sarah Johnson Alexei Tulin Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes Frontiers in Endocrinology PARP-1 metabolic genes developmental genes gene expression PARP-1 domains |
| title | Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes |
| title_full | Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes |
| title_fullStr | Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes |
| title_full_unstemmed | Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes |
| title_short | Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes |
| title_sort | cooperative targeting of parp 1 domains to regulate metabolic and developmental genes |
| topic | PARP-1 metabolic genes developmental genes gene expression PARP-1 domains |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1152570/full |
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