Dynamic changes in chromatin states during specification and differentiation of adult intestinal stem cells
| Autor: | Christina Krienke, Juri Kazakevych, Berith Messner, Sergi Sayols, Natalia Soshnikova |
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| Rok vydání: | 2017 |
| Předmět: |
Male
inorganic chemicals 0301 basic medicine Transcription Genetic Cellular differentiation Mice Transgenic Biology digestive system Chromatin remodeling Histones Mice 03 medical and health sciences Genetics Animals Cell Lineage Gene Silencing Epigenetics Intestinal Mucosa Embryonic Stem Cells Gene regulation Chromatin and Epigenetics fungi Cell Differentiation DNA Methylation Chromatin Assembly and Disassembly Embryo Mammalian Embryonic stem cell Chromatin Intestines Adult Stem Cells Enterocytes 030104 developmental biology DNA methylation Stem cell Adult stem cell |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Epigenetic mechanisms, including chromatin structure, chromatin dynamics and histone modifications play an important role for maintenance and differentiation of pluripotent embryonic stem cells. However, little is known about the molecular mechanisms of adult stem cell specification and differentiation. Here, we used intestinal stem cells (ISCs) as a model system to reveal the epigenetic changes coordinating gene expression programs during these processes. We found that two distinct epigenetic mechanisms participate in establishing the transcriptional program promoting ISC specification from embryonic progenitors. A large number of adult ISC signature genes are targets of repressive DNA methylation in embryonic intestinal epithelial progenitors. On the other hand, genes essential for embryonic development acquire H3K27me3 and are silenced during ISC specification. We also show that the repression of ISC signature genes as well as the activation of enterocyte specific genes is accompanied by a global loss of H2A.Z during ISCs differentiation. Our results reveal that, already during ISC specification, an extensive remodeling of chromatin both at promoters and distal regulatory elements organizes transcriptional landscapes operating in differentiated enterocytes, thus explaining similar chromatin modification patterns in the adult gut epithelium. |
| Databáze: | OpenAIRE |
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