Project description:Next Generation Sequencing Facilitates Quantitative Analysis of NB4 cells transduced with control or JMJD3-expression vector. JMJD3, a stress-inducible H3K27 demethylase, plays a critical regulatory role in the initiation and progression of malignant hematopoiesis. However, how this histone modifier effects in a cell type-dependent manner remains unclear. Here, we show that in contrast to its oncogenic effect in preleukemia state and lymphoid malignancies, JMJD3 relieves the differentiation-arrest of certain subtypes (such as M2 and M3) of acute myeloid leukemia (AML) cells. RNA-sequencing and ChIP-PCR analyses revealed that JMJD3 exerts anti-AML effect by directly modulating H3K4 and H3K27 methylation levels to activate the expression of a number of key myelopoietic regulatory genes. Mechanistic exploration identified a physical and functional association of JMJD3 with C/EBPb that presides the regulatory network of JMJD3. Thus, the leukemia regulatory role of JMJD3 varies in a disease phase- and lineage-dependent manner, and acts as a potential oncorepressor in certain subsets of AML largely by coupling to C/EBPb-centered myelopoietic program.
Project description:Next Generation Sequencing Facilitates Quantitative Analysis of HL-60 cells transduced with control or JMJD3-expression vector, and HL-60 parental and JMJD3 knockout cells
Project description:Gene expression profiles were compared between wild-type and Jmjd3-/- embryos at E9.5 when mRNAs of posterior Hox genes are upregulated, because Jmjd3-/- mice embryos showed homeotic transformation. As expected, mRNAs of Hoxd10 and Hod11 were decreased in Jmjd3-/- embryos. Moreover, gene onthology (GO) analyses identified down-regulated genes (FC>1.5) in Jmjd3-/- embryos were “multicellular organismal development” and “developmental process”.
Project description:Gene expression profiles were compared between wild-type and Jmjd3-/- embryos at E9.5 when mRNAs of posterior Hox genes are upregulated, because Jmjd3-/- mice embryos showed homeotic transformation. As expected, mRNAs of Hoxd10 and Hod11 were decreased in Jmjd3-/- embryos. Moreover, gene onthology (GO) analyses identified down-regulated genes (FC>1.5) in Jmjd3-/- embryos were M-bM-^@M-^\multicellular organismal developmentM-bM-^@M-^] and M-bM-^@M-^\developmental processM-bM-^@M-^]. Gene expressions in wild-type and Jmjd3-/- posterior half of embryos at E9.5 were examined. Two independent RNA samples of each genotypes were used to verify the reproducibility of the microarray analyses.
Project description:Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we identify Jumonji-D3 (JMJD3/KDM6B) histone demethylase as a key epigenetic activator of hepatic autophagy. Upon fasting-induced fibroblast growth factor-21 (FGF21) signaling, JMJD3 epigenetically upregulated global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increased its nuclear localization and interaction with the nuclear receptor PPARto transcriptionally activate autophagy. Chronic administration of FGF21 in obese mice improved defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and KL were substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to explore ChIPseq results for LDB1 in NB4 cell line.
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to explore CUT-TAG results for LDB1 in NB4 cell line.