Functional analysis of histone demethylase Jmjd2b on lipopolysaccharide-treated murine neural stem cells (NSCs).
Neural stem cell (NSC) neurogenesis is the formation of new neurons by which the brain maintains its lifelong plasticity in response to extrinsic and intrinsic changes. Here, we show the effect of lipopolysaccharides (LPS) as an in vitro model of inflammation on NSCs to determine whether the inflammatory mediators can epigenetically affect NSCs and alter their proliferation and differentiation abilities. To study the effect of LPS on NSCs, we used an immortalized mouse neuroectodermal stem cell line, NE-4C. We found that Jmjd2b, histone-3 lysine-9 di-/tri-methyl (H3K9me2/3) demethylase, is functional following LPS treatment and is crucial in multiple signaling pathways and biological processes. The global gene expression levels were detected in Jmjd2b-knockdown (kd) NE-4C cells and in LPS-stimulated Jmjd2b-kd NE-4C cells using an Affymetrix GeneChip(®) Mouse Gene 1.0 ST Array. In addition, the datasets were analyzed using MetaCore Pathway Analysis (GeneGo). The attenuation of Jmjd2b in NE-4C cells significantly affected the p65, iNOS, Bcl2, and TGF-β expression levels and had downstream effects on related signaling pathways. In addition, chromatin immunoprecipitation revealed that Jmjd2b-kd could inhibit the Notch1, IL-1β, and IL-2 genes by recruiting repressive H3K9me3 to their promoters. Moreover, this study highlights Jmjd2b role in LPS-mediated inflammation, which suggests an epigenetic regulation in NE-4C cells. Finally, this study establishes novel Jmjd2b targets that potentiate a biological rationale involving Jmjd2b in NSC inflammation.
Division of Molecular & Life Science, Hanyang University, 1271 Sa 3-dong, Gyeonggi-do, Ansan 426-791, Korea. nando.hu@gmail.com
Nando Dulal
ND
Das
Mi Ran
MR
Choi
Kyoung Hwa
KH
Jung
Ji Hyun
JH
Park
Hyung Tae
HT
Lee
Amitabh
A
Das
Seung Hyun
SH
Kim
Young Gyu
YG
Chai
D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic / Q000187:drug effects*; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D014212:Tretinoin; D056484:Jumonji Domain-Containing Histone Demethylases; C511781:Kdm4b protein, mouse