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.
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.
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.
Project description:BackgroundHistone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation.ResultsGiven the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue.ConclusionsOverall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.