JMJD3 facilitates C/EBPβ-centered transcriptional program to exert oncorepressor activity in AML

Yu, Shanhe; Zhu, Kunfu; Chen, Juan; Liu, Xiang-Zhen; Xu, Pengfei; Zhang, Wu; Li, Yan; Guo, Hongbo; Zhu, Jiang

doi:10.1038/s41467-018-05548-z

Cited by 56 publications

(49 citation statements)

References 68 publications

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“…JMJD3 is an H3K27me3 demethylase ( 17 ); however, we also observed changes in H3K4me3 in the promoter region of C/EBPB. JMJD3 has recently been shown to impact H3K4me3 levels in human acute myeloid leukemia (AML) cells ( 32 ). This may not fully explain the epigenetic changes in our model, and other epigenetic mediators, including other non-methyl modifications, might influence gut microbiota–mediated communication with the bone marrow.…”

Section: Resultsmentioning

confidence: 99%

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

Burgess

Leslie

et al. 2020

Journal of Clinical Investigation

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The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with the intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity. Introduction of C . scindens into the gut microbiota epigenetically altered and expanded bone marrow granulocyte-monocyte progenitors (GMPs) and resulted in increased intestinal neutrophils with subsequent challenge with E . histolytica . Introduction of C . scindens alone was sufficient to expand GMPs in gnotobiotic mice. Adoptive transfer of bone marrow from C . scindens –colonized mice into naive mice protected against amebic colitis and increased intestinal neutrophils. Children without E . histolytica diarrhea also had a higher abundance of Lachnoclostridia. Lachnoclostridia C . scindens can metabolize the bile salt cholate, so we measured deoxycholate and discovered that it was increased in the sera of C . scindens –colonized specific pathogen–free and gnotobiotic mice, as well as in children protected from amebiasis. Administration of deoxycholate alone increased GMPs and provided protection from amebiasis. We elucidated a mechanism by which C . scindens and the microbially metabolized bile salt deoxycholic acid alter hematopoietic precursors and provide innate protection from later infection with E . histolytica .

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Section: Resultsmentioning

confidence: 99%

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

Burgess

Leslie

et al. 2020

Journal of Clinical Investigation

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“…Approximately 5 μg of total RNA was used to prepare an mRNA library for paired-end sequencing (2 × 150 bp read length) on a NovaSeq sequencing system (Illumina HiSeq. 4000, San Diego, USA) according to a previous study [30]. The capra-hircus gene annotation list was used as background (https://www.ncbi.nlm.nih.gov/genome/?term= txid9925[orgn]).…”

Section: Transcriptomics Analysismentioning

confidence: 99%

High rumen degradable starch decreased goat milk fat via trans-10, cis-12 conjugated linoleic acid-mediated downregulation of lipogenesis genes, particularly, INSIG1

Shen

et al. 2020

J Animal Sci Biotechnol

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Background: Starch is an important substance that supplies energy to ruminants. To provide sufficient energy for high-yielding dairy ruminants, they are typically fed starch-enriched diets. However, starch-enriched diets have been proven to increase the risk of milk fat depression (MFD) in dairy cows. The starch present in ruminant diets could be divided into rumen-degradable starch (RDS) and rumen escaped starch (RES) according to their different degradation sites (rumen or intestine). Goats and cows have different sensitivities to MFD. Data regarding the potential roles of RDS in milk fat synthesis in the mammary tissue of dairy goats and in regulating the occurrence of MFD are limited. Results: Eighteen Guanzhong dairy goats (day in milk = 185 ± 12 d) with similar parity, weight, and milk yield were selected and randomly assigned to one of three groups (n = 6), which were fed an LRDS diet (Low RDS = 20.52%), MRDS diet (Medium RDS = 22.15%), or HRDS diet (High RDS = 24.88%) for 5 weeks. Compared with that of the LRDS group, the milk fat contents in the MRDS and HRDS groups significantly decreased. The yields of short-, mediumand long-chain fatty acids decreased in the HRDS group. Furthermore, increased RDS significantly decreased ruminal B. fibrisolvens and Pseudobutyrivibrio abundances and increased the trans-10, cis-12 conjugated linoleic acid (CLA) and trans-10 C18:1 contents in the rumen fluid. A multiomics study revealed that the HRDS diet affected mammary lipid metabolism down-regulation of ACSS2, MVD, AGPS, SCD5, FADS2, CERCAM, SC5D, HSD17B7, HSD17B12, ATM, TP53RK, GDF1 and LOC102177400. Remarkably, the significant decrease of INSIG1, whose expression was depressed by trans-10, cis-12 CLA, could reduce the activity of SREBP and, consequently, downregulate the downstream gene expression of SREBF1. Conclusions: HRDS-induced goat MFD resulted from the downregulation of genes involved in lipogenesis, particularly, INSIG1. Specifically, even though the total starch content and the concentrate-to-fiber ratio were the same as those of the high-RDS diet, the low and medium RDS diets did not cause MFD in lactating goats.

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“…We performed ChIP assays essentially as described previously (36). In brief, we harvested and crosslinked the cells with 1% formaldehyde for 10 min at room temperature.…”

Section: Chromatin Immunoprecipitation (Chip)mentioning

confidence: 99%

KDM5C Represses FASN-Mediated Lipid Metabolism to Exert Tumor Suppressor Activity in Intrahepatic Cholangiocarcinoma

et al. 2020

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Background: KDM5C is a histone H3K4-specific demethylase, which has multiple biological functions during development and disease. However, the role of KDM5C in intrahepatic cholangiocarcinoma (ICC) remains unknown. Methods: Expression levels of KDM5C in ICC patients were determined by qRT-PCR, western blotting and immunohistochemical assay. The functions of KDM5C in cell proliferation and invasion were determined in human ICC cells and mouse xenograft model using KDM5C overexpression and knockdown strategies in vivo. RNA-seq analysis was applied to investigate the transcriptional program of KDM5C. In addition, ChIP-qPCR was used to determine the regulation of FASN by KDM5C. Results: Here, we show that KDM5C was downregulated in human ICC, where its diminished expression was associated with poor prognosis. ICC cell proliferation and invasion were inhibited by KDM5C overexpression. Moreover, KDM5C suppressed ICC proliferation and metastasis in vivo. RNA-sequencing showed that KDM5C inhibits key signal pathways of cell proliferation, cell invasion and fatty acid metabolism. ChIP-qPCR revealed that overexpression of KDM5C led to the reduction of H3K4me3 on the promoter and the corresponding downregulation of the expression of FASN, which represents the major target gene of KDM5C to mediate the proliferation and invasion of ICC cells. Conclusions: Our results revealed the role of KDM5C as a novel tumor suppressor in ICC largely by repressing FASN-mediated lipid acid metabolism and thus KDM5C may contribute to the pathogenesis of ICC.

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JMJD3 facilitates C/EBPβ-centered transcriptional program to exert oncorepressor activity in AML

Cited by 56 publications

References 68 publications

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

High rumen degradable starch decreased goat milk fat via trans-10, cis-12 conjugated linoleic acid-mediated downregulation of lipogenesis genes, particularly, INSIG1

KDM5C Represses FASN-Mediated Lipid Metabolism to Exert Tumor Suppressor Activity in Intrahepatic Cholangiocarcinoma

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