Thalheim, Torsten ORCID: 0000-0001-5489-7405, Hopp, Lydia, Herberg, Maria, Siebert, Susann, Kerner, Christiane, Quaas, Marianne, Schweiger, Michal R., Aust, Gabriela and Galle, Joerg (2020). Fighting Against Promoter DNA Hyper-Methylation: Protective Histone Modification Profiles of Stress-Resistant Intestinal Stem Cells. Int. J. Mol. Sci., 21 (6). BASEL: MDPI. ISSN 1422-0067
Full text not available from this repository.Abstract
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.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-342044 | ||||||||||||||||||||||||||||||||||||||||
DOI: | 10.3390/ijms21061941 | ||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Int. J. Mol. Sci. | ||||||||||||||||||||||||||||||||||||||||
Volume: | 21 | ||||||||||||||||||||||||||||||||||||||||
Number: | 6 | ||||||||||||||||||||||||||||||||||||||||
Date: | 2020 | ||||||||||||||||||||||||||||||||||||||||
Publisher: | MDPI | ||||||||||||||||||||||||||||||||||||||||
Place of Publication: | BASEL | ||||||||||||||||||||||||||||||||||||||||
ISSN: | 1422-0067 | ||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/34204 |
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