The genome-wide targeting of H3K18la in H1299 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE207814 | GEO | 2023/07/30
REPOSITORIES: GEO
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Project description:Histone lactylation has been served as a novel epigenetic modification that directly stimulates gene transcription from chromatin. In order to study the regulatory mechanisms of H3K18la in non-small cell lung cancer (NSCLC), we performed ChIP-Seq to identify its target genes in NCI-H1299 cell lines.
2024-08-06 | GSE245990 | GEO
Project description:The genome-wide targeting of H3K18la in H1299 cells
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Project description:Cancer-augmented lactogenesis has been described by the Warburg effect, and is associated with several major hallmarks of neoplasia. However, the non-metabolic functions of elevated lactate in physiology and disease remain unknown. Here we report histone lysine lactylation as a new type of epigenetic mechanism and as a functional destination for lactate. Histone lactylation is induced under glycolytic conditions such as hypoxia and M1 macrophage polarization. In the late phase of M1 macrophage polarization, increases in histone lactylation but not acetylation mark M2-like genes for activation. Our findings suggest a feedback mechanism of the innate immune system to switch from proinflammation to resolution through histone Kla-associated gene expression. This mechanism is implemented by the coopted function of lactate and histone lactylation in metabolism and epigenetics. Together, our study opens a new avenue for understanding function of lactate and glycolysis underlined diverse pathophysiological conditions.
2019-08-06 | GSE115354 | GEO
Project description:Tumor cells are known for excessive lactate production, due to Warburg effect, and transcriptional dysregulation. However, how lactate influences the epigenetic modifications at a genome-wide level and its impact on gene transcription in tumor cell remains unclear. Addressing this gap, we analyzed genome-wide modification of H3K18 lactylation (H3K18la) in T-cell acute lymphoblastic leukemia (T-ALL). Integrated analysis with histone modifications with established functions show the H3K18la is mainly involved in active regulation of gene transcription. We report increased lactate and H3K18la modification levels in T-ALL as compared to normal T cells. We observe clusters of H3K18la modifications in patterns reminiscent of super-enhancers. We show a notable shift of genome-wide H3K18la modification from T cell immunity in normal T cells to leukemogenesis in T-ALL, correlating with altered gene transcription profiles. By disrupting H3K18la modification, we uncover both synergetic and divergent changes between H3K18la and H3K27ac modifications, suggesting the H3K18la and H3K27ac modifications may have specific regulation mechanisms correspondingly. These findings expand our understanding of metabolic disruptions involvement in transcription dysregulation through epigenetic changes in T-ALL, and emphasize the collective importance of histone modifications in maintaining oncogenic epigenetic stability.
2024-05-20 | GSE263697 | GEO
Project description:Tumor cells are known for excessive lactate production, due to Warburg effect, and transcriptional dysregulation. However, how lactate influences the epigenetic modifications at a genome-wide level and its impact on gene transcription in tumor cell remains unclear. Addressing this gap, we analyzed genome-wide modification of H3K18 lactylation (H3K18la) in T-cell acute lymphoblastic leukemia (T-ALL). Integrated analysis with histone modifications with established functions show the H3K18la is mainly involved in active regulation of gene transcription. We report increased lactate and H3K18la modification levels in T-ALL as compared to normal T cells. We observe clusters of H3K18la modifications in patterns reminiscent of super-enhancers. We show a notable shift of genome-wide H3K18la modification from T cell immunity in normal T cells to leukemogenesis in T-ALL, correlating with altered gene transcription profiles. By disrupting H3K18la modification, we uncover both synergetic and divergent changes between H3K18la and H3K27ac modifications, suggesting the H3K18la and H3K27ac modifications may have specific regulation mechanisms correspondingly. These findings expand our understanding of metabolic disruptions involvement in transcription dysregulation through epigenetic changes in T-ALL, and emphasize the collective importance of histone modifications in maintaining oncogenic epigenetic stability.
2024-05-31 | GSE263584 | GEO
Project description:We profiled the genome-wide distribution of H3K18la in samples originating from 6 different in vitro and in vivo mouse samples, representing 3 tissues: embryonic stem cells, macrophages and skeletal muscle as well as in human skeletal muscle and compared them to the profiles of other well-established histone modifications as well as gene expression patterns. Globally, we found that H3K18la profiles resemble H3K27ac profiles better than any other investigated hPTM, including H3K4me3, but that they do not copy them. For all samples, H3K18la marked active CGI promoters of highly expressed genes which were remarkably shared across the different mouse tissues and which contained many housekeeping genes. Promoter H3K18la levels correlated positively to both H3K27ac and H3K4me3 levels as well as to gene expression levels. In addition, we found that H3K18la is enriched at tissue-type specific, active enhancers, which are particularly tissue-type-specific, especially when compared to the H3K18la-marked promoter regions. Accordingly, enhancer H3K18la levels correlate positively to the expression of their nearest genes. Additionally, genes closest to enhancers with high H3K18la levels predominantly consist of tissue-type specific marker genes. Overall, we showed that H3K18la is not only a marker for active promoters, but that it also marks active enhancers, and this both in embryonic tissues and differentiated tissues, and both in mouse and in human.
2022-09-14 | GSE195859 | GEO
Project description:We profiled the genome-wide distribution of H3K18la in samples originating from 6 different in vitro and in vivo mouse samples, representing 3 tissues: embryonic stem cells, macrophages and skeletal muscle as well as in human skeletal muscle and compared them to the profiles of other well-established histone modifications as well as gene expression patterns. Globally, we found that H3K18la profiles resemble H3K27ac profiles better than any other investigated hPTM, including H3K4me3, but that they do not copy them. For all samples, H3K18la marked active CGI promoters of highly expressed genes which were remarkably shared across the different mouse tissues and which contained many housekeeping genes. Promoter H3K18la levels correlated positively to both H3K27ac and H3K4me3 levels as well as to gene expression levels. In addition, we found that H3K18la is enriched at tissue-type specific, active enhancers, which are particularly tissue-type-specific, especially when compared to the H3K18la-marked promoter regions. Accordingly, enhancer H3K18la levels correlate positively to the expression of their nearest genes. Additionally, genes closest to enhancers with high H3K18la levels predominantly consist of tissue-type specific marker genes. Overall, we showed that H3K18la is not only a marker for active promoters, but that it also marks active enhancers, and this both in embryonic tissues and differentiated tissues, and both in mouse and in human.
2022-09-14 | GSE195856 | GEO
Project description:We profiled the genome-wide distribution of H3K18la in samples originating from 6 different in vitro and in vivo mouse samples, representing 3 tissues: embryonic stem cells, macrophages and skeletal muscle as well as in human skeletal muscle and compared them to the profiles of other well-established histone modifications as well as gene expression patterns. Globally, we found that H3K18la profiles resemble H3K27ac profiles better than any other investigated hPTM, including H3K4me3, but that they do not copy them. For all samples, H3K18la marked active CGI promoters of highly expressed genes which were remarkably shared across the different mouse tissues and which contained many housekeeping genes. Promoter H3K18la levels correlated positively to both H3K27ac and H3K4me3 levels as well as to gene expression levels. In addition, we found that H3K18la is enriched at tissue-type specific, active enhancers, which are particularly tissue-type-specific, especially when compared to the H3K18la-marked promoter regions. Accordingly, enhancer H3K18la levels correlate positively to the expression of their nearest genes. Additionally, genes closest to enhancers with high H3K18la levels predominantly consist of tissue-type specific marker genes. Overall, we showed that H3K18la is not only a marker for active promoters, but that it also marks active enhancers, and this both in embryonic tissues and differentiated tissues, and both in mouse and in human.
2022-09-14 | GSE195854 | GEO
Project description:Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. Interestingly, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on TSSs and the regulated Kla can facilitate in signaling pathways and progress of tumorigenesis. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.
2024-01-16 | GSE239656 | GEO
Project description:Lysine lactylation (Kla) is a new type of histone mark implicated in the regulation of various functional processes such as transcription. However, how this histone mark acts in cancers remains unexplored due in part to a lack of knowledge about its reader proteins. Here, we observe that cervical cancer (CC) cells undergo metabolic reprogram by which lactate accumulation and thereby boost histone lactylation, particularly H3K14la. Utilizing a multivalent photoaffinity probe in combination with quantitative proteomics approach, we identify DPF2 as a candidate target of H3K14la. Biochemical studies as well as CUT&Tag analysis reveal that DPF2 is capable of binding to H3K14la, and co-localizes with it on promoters of oncogenic genes. Notably, disrupting the association between DPF2 and histone lactylation through structure-guided mutation blunts those cancer-related gene expression along with cell survival. Together, our findings reveal DPF2 as a bona fide H3K14la effector that couples histone lactylation to gene transcription and cell survival, offering insight into how histone Kla engages in transcription and tumorigenesis.
2024-06-17 | GSE267109 | GEO