RRC ID 57189
Author Suong DNA, Shimaji K, Pyo JH, Park JS, Yoshida H, Yoo MA, Yamaguchi M.
Title Overexpression of dJmj differentially affects intestinal stem cells and differentiated enterocytes.
Journal Cell Signal
Abstract Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo. Overexpression of dJmj in intestinal stem cells/enteroblasts (ISCs/EBs) induces cell-autonomous ISC proliferation followed by differentiation, that is controlled by the Notch and EGFR pathway. In contrast, overexpression of dJmj in enterocytes (ECs) resulted in activation of the JNK pathway in ECs followed by the induction of apoptosis. Activated JNK increased the level of Yorkie in ECs and induced the reduction of Upd proteins and EGFR ligands, which activated the JAK/STAT and EGFR pathway in both ISCs and EBs to promote ISC proliferation. The Notch signaling pathway appears to be highly activated to support the differentiation of EBs to ECs. Thus, the combination of these signaling pathways caused by ECs-specific dJmj-overexpression induced non-cell-autonomous ISC proliferation and differentiation. Surprisingly, these effects did not relate to H3K27me3 status, likely represented PRC2 activity, in cells that overexpressed dJmj. Instead of this, the disappearance of H3K27me3 in ISC/EB-specific overexpressed dJmj suggested a possible PRC2-independent role of dJmj in regulating chromatin structure.
Volume 42
Pages 194-210
Published 2018-1-1
DOI 10.1016/j.cellsig.2017.10.017
PII S0898-6568(17)30286-3
PMID 29102770
MeSH Animals Apoptosis / genetics Cell Differentiation Cell Proliferation Chromatin / chemistry Chromatin / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Enterocytes / cytology Enterocytes / metabolism* ErbB Receptors / genetics ErbB Receptors / metabolism Gene Expression Regulation, Developmental* Histone-Lysine N-Methyltransferase / genetics* Histone-Lysine N-Methyltransferase / metabolism Histones / genetics Histones / metabolism Intestinal Mucosa / metabolism* Intestines / cytology Intestines / growth & development MAP Kinase Signaling System Nuclear Proteins / genetics Nuclear Proteins / metabolism Receptors, Invertebrate Peptide / genetics Receptors, Invertebrate Peptide / metabolism Receptors, Notch / genetics Receptors, Notch / metabolism STAT Transcription Factors / genetics STAT Transcription Factors / metabolism Stem Cells / cytology Stem Cells / metabolism* Trans-Activators / genetics Trans-Activators / metabolism Transcription Factors / genetics* Transcription Factors / metabolism YAP-Signaling Proteins
IF 3.388
Times Cited 1