ENL reads histone β-hydroxybutyrylation to modulate gene transcription (RNA-Seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1106487 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28852626_1.fastq.gz | Fastqsanger.gz | |||
| SRR28852626_2.fastq.gz | Fastqsanger.gz | |||
| SRR28852627_1.fastq.gz | Fastqsanger.gz | |||
| SRR28852627_2.fastq.gz | Fastqsanger.gz |
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Project description:Histone modifications are typically recognized by chromatin-binding protein modules (referred to as “readers”) to mediate fundamental processes such as transcription. Lysine β-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap must be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation leads to the suppressed expression of the gene like MYC that drives cell proliferation.
2024-05-06 | GSE266269 | GEO
Project description:Histone modifications are typically recognized by chromatin-binding protein modules (referred to as “readers”) to mediate fundamental processes such as transcription. Lysine β-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap must be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation leads to the suppressed expression of the gene like MYC that drives cell proliferation.
2024-05-06 | GSE266268 | GEO
Project description:ENL reads histone β-hydroxybutyrylation to modulate gene transcription (CUT&Tag)
| PRJNA1106475 | ENA
Project description:Histone modifications are typically recognized by chromatin-binding protein modules (referred to as 'readers') to mediate fundamental processes such as transcription. Lysine β-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap should be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark, and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation led to the suppressed expression of genes such MYC that drive cell proliferation. Together, our work offered a chemoproteomics approach and identified ENL as a novel histone β-hydroxybutyrylation effector that regulates gene transcription, providing new insight into the regulation mechanism and function of histone Kbhb.
| S-EPMC11417371 | biostudies-literature
Project description:Identification of hPTM binder through the chemoproteomic approach
2024-06-26 | PXD051689 | Pride
Project description:Histone lysine β-hydroxybutyrylation (Kbhb) links ketone metabolism to gene transcription. However, the regulatory mechanism that kenogenesis-derived β-hydroxybutyrate, present throughout cells at low concentration, orchestrates this histone mark remains largely unknown. Here, we unveil a KAT7-ACSS2 module in which ACSS2 locally generates β-hydroxybutyryl-CoA (BHB-CoA), thereby bolsters histone Kbhb through fueling KAT7. Specifically, we show that KAT7 serves as a histone β-hydroxybutyryltransferase that prefers to modulate β-hydroxybutyrylation on histone H3 lysine 9 (H3K9bhb) by utilizing ACSS2-directed BHB-CoA. Moreover, ACSS2 senses β-hydroxybutyrate and translocates into the nucleus wherein it binds to and colocalizes with KAT7 at gene promoter regions. We further show that KAT7 coupled with ACSS2 regulates specific activation of genes associated with tumor cell survival through histone Kbhb. Collectively, our findings reveal that KAT7-ACSS2 module promotes histone β-hydroxybutyrylation by providing BHB-CoA locally, highlighting the importance of linking metabolic enzyme ACSS2 and KAT7 for histone Kbhb as well as offering insight into the regulatory mechanism of cellular metabolite on epigenetic modification and gene transcription.
2025-07-02 | GSE267130 | GEO
Project description:Histone lysine β-hydroxybutyrylation (Kbhb) links ketone metabolism to gene transcription. However, the regulatory mechanism that kenogenesis-derived β-hydroxybutyrate, present throughout cells at low concentration, orchestrates this histone mark remains largely unknown. Here, we unveil a KAT7-ACSS2 module in which ACSS2 locally generates β-hydroxybutyryl-CoA (BHB-CoA), thereby bolsters histone Kbhb through fueling KAT7. Specifically, we show that KAT7 serves as a histone β-hydroxybutyryltransferase that prefers to modulate β-hydroxybutyrylation on histone H3 lysine 9 (H3K9bhb) by utilizing ACSS2-directed BHB-CoA. Moreover, ACSS2 senses β-hydroxybutyrate and translocates into the nucleus wherein it binds to and colocalizes with KAT7 at gene promoter regions. We further show that KAT7 coupled with ACSS2 regulates specific activation of genes associated with tumor cell survival through histone Kbhb. Collectively, our findings reveal that KAT7-ACSS2 module promotes histone β-hydroxybutyrylation by providing BHB-CoA locally, highlighting the importance of linking metabolic enzyme ACSS2 and KAT7 for histone Kbhb as well as offering insight into the regulatory mechanism of cellular metabolite on epigenetic modification and gene transcription.
2025-07-02 | GSE267129 | GEO
Project description:Background: Previously, we demonstrated that the ketone body, β-hydroxybutyrate, is a potent antihypertensive and reno-protective metabolite in Dahl Salt-Sensitive rats. However, the mechanism by which β-hydroxybutyrate confers these beneficial effects is understudied. Here we focused on determining whether the reno-protective effect of β-hydroxybutyrate is due to its known ability to epigenetically remodel chromatin via histone β-hydroxybutyrylation. Methods: We used the same animal protocol previously used for the discovery of the renoprotective effect of β-hydroxybutyrate. Briefly, post-weaning, male and female Dahl Salt-Sensitive rats were split into two groups and supplemented with or without 1,3-Butanediol for 6 weeks. At euthanasia, circulating β-hydroxybutyrate was quantitated. Renal homogenates were examined for histone 3 lysine 9 β-hydroxybutyrylation, chromatin occupancy, transcriptomic and proteomic profiles with validations. Results: Rats supplemented with 1,3-butanediol had higher circulating β-hydroxybutyrate, renal histone β-hydroxybutyrylation and significant remodeling of chromatin. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. The most highly upregulated gene actively transcribed and translated was 3-hydroxy-3-methyglutaryl CoA Synthase 2 (Hmgcs2), a gene responsible for the biosynthesis of β-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures contained immune function genes, protein tyrosine phosphatase receptor type C (Ptprc) and lymphocyte cytosolic protein 1 (Lcp1), which were suppressed. Conclusions: These results reveal that renal epigenetic histone β-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly and contribute to renoprotection in the hypertensive Dahl rat.
2025-06-06 | GSE298452 | GEO
Project description:Background: Previously, we demonstrated that the ketone body, β-hydroxybutyrate, is a potent antihypertensive and reno-protective metabolite in Dahl Salt-Sensitive rats. However, the mechanism by which β-hydroxybutyrate confers these beneficial effects is understudied. Here we focused on determining whether the reno-protective effect of β-hydroxybutyrate is due to its known ability to epigenetically remodel chromatin via histone β-hydroxybutyrylation. Methods: We used the same animal protocol previously used for the discovery of the renoprotective effect of β-hydroxybutyrate. Briefly, post-weaning, male and female Dahl Salt-Sensitive rats were split into two groups and supplemented with or without 1,3-Butanediol for 6 weeks. At euthanasia, circulating β-hydroxybutyrate was quantitated. Renal homogenates were examined for histone 3 lysine 9 β-hydroxybutyrylation, chromatin occupancy, transcriptomic and proteomic profiles with validations. Results: Rats supplemented with 1,3-butanediol had higher circulating β-hydroxybutyrate, renal histone β-hydroxybutyrylation and significant remodeling of chromatin. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. The most highly upregulated gene actively transcribed and translated was 3-hydroxy-3-methyglutaryl CoA Synthase 2 (Hmgcs2), a gene responsible for the biosynthesis of β-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures contained immune function genes, protein tyrosine phosphatase receptor type C (Ptprc) and lymphocyte cytosolic protein 1 (Lcp1), which were suppressed. Conclusions: These results reveal that renal epigenetic histone β-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly and contribute to renoprotection in the hypertensive Dahl rat.
2025-06-06 | GSE298451 | GEO
Project description:Studies have shown the therapeutic effects of a ketogenic diet (KD) on epilepsy, but the effect of KD on drug reinstatement is largely unclear. This study aims to investigate whether KD consumption possesses therapeutic potential for cocaine reinstatement and the molecular mechanism. We find that KD significantly reduce cocaine induced-reinstatement in mice, which is accompanied by a markedly elevated level of β-hydroxybutyrate (β-OHB), the most abundant ketone body, in the hippocampus. The underlying mechanism is that β-OHB posttranslationally modify CaMKII-α with β-hydroxybutyrylation, resulting in significant inhibition of T286 autophosphorylation and downregulation of CaMKII activity. Collectively, our results reveal that β-hydroxybutyrylation is a posttranslational modification of CaMKII-α that plays a critical role in mediating the effect of KD consumption in reducing cocaine reinstatement.
2022-11-30 | PXD037321 | Pride