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  • Dynamic changes in chromatin states during specification and differentiation of adult intestinal stem cells.

Dynamic changes in chromatin states during specification and differentiation of adult intestinal stem cells.

Nucleic acids research (2017-03-24)
Juri Kazakevych, Sergi Sayols, Berith Messner, Christina Krienke, Natalia Soshnikova
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Millipore
EZview Red Protein A Affinity Gel
Sigma-Aldrich
ChIPAb+ Trimethyl-Histone H3 (Lys27) - ChIP Validated Antibody and Primer Set, from rabbit, purified by using Protein A
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Anti-trimethyl-Histone H3 (Lys4) Antibody, Upstate®, from rabbit
Millipore
EZview Red Protein G Affinity Gel