Aberrant DNA methylation in stem cells is a hallmark of aging and tumor development.
Recently, we have suggested that promoter DNA hyper-methylation originates in DNA repair and
that even successful DNA repair might confer this kind of epigenetic long-term change. Here, we ask
for interrelations between promoter DNA methylation and histone modification changes observed in
the intestine weeks after irradiation and/or following Msh2 loss. We focus on H3K4me3 recruitment
to the promoter of H3K27me3 target genes. By RNA- and histone ChIP-sequencing, we demonstrate
that this recruitment occurs without changes of the average gene transcription and does not involve
H3K9me3. Applying a mathematical model of epigenetic regulation of transcription, we show that
the recruitment can be explained by stronger DNA binding of H3K4me3 and H3K27me3 histone
methyl-transferases as a consequence of lower DNA methylation. This scenario implicates stable
transcription despite of H3K4me3 recruitment, in agreement with our RNA-seq data. Following
several kinds of stress, including moderate irradiation, stress-sensitive intestinal stem cell (ISCs)
are known to become replaced by more resistant populations. Our simulation results suggest that
the stress-resistant ISCs are largely protected against promoter hyper-methylation of H3K27me3
target genes.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88784 |
| Date | 29 December 2023 |
| Creators | Thalheim, Torsten, Hopp, Lydia, Herberg, Maria, Siebert, Susann, Kerner, Christiane, Quaas, Marianne, Schweiger, Michal R., Aust, Gabriela, Galle, Joerg |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1941, 10.3390/ijms21061941 |
Page generated in 0.014 seconds