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2017 ; 45
(10
): 5770-5784
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Dynamic changes in chromatin states during specification and differentiation of
adult intestinal stem cells
#MMPMID28334816
Kazakevych J
; Sayols S
; Messner B
; Krienke C
; Soshnikova N
Nucleic Acids Res
2017[Jun]; 45
(10
): 5770-5784
PMID28334816
show ga
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.