JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

The gene expressions of codeinone reductase (COR) and berberine bridge enzyme (BBE) in Papaver somniferum were blocked by RNA hairpin of RNA interference (RNAi). The complete sequences of COR and BBE genes were cloned by reverse transcription-polymerase chain reaction (RT-PCR), the results of homology comparison revealed that the cloned COR and BBE genes had high homology with the other gene family members reported in the GenBank. The target sequences of COR and BBE genes were screened in accordance with the design principle of RNAi, a 643 bp fusion gene was obtained by the method of overlapping PCR, then plant expression vector ihpRNA was constructed based on intermediate vector pHANNIBAL and plant expression vector pCEPSPS. With that 78 transgenic plants were obtained through Agrobacterium-mediated and 17 positive plants were screened by PCR, that could initially indicate that the target fragments of COR and BBE gene had been integrated into tobacco genome.
Artificial Gene Fusion ; Genetic Vectors ; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases ; genetics ; Oxidoreductases, N-Demethylating ; genetics ; Papaver ; enzymology ; genetics ; Plants, Genetically Modified ; enzymology ; genetics ; RNA Interference ; RNA, Small Interfering ; Tobacco ; genetics ; Transformation, Genetic

OBJECTIVETo evaluate the influence of individual genetic polymorphisms of metabolic enzymes on urinary styrene metabolites.

METHODS58 workers occupationally exposed to styrene were divided into the high exposure group (≥ 100 mg/m³) and the low exposure group (< 100 mg/m³). The microfluidic chip technology was used to determine the SNPs of CYP2B6, CYP2D6 and GSTP1 and the influence of gene polymorphisms on the metabolism of styrene was statistically analyzed.

RESULTSThe level of urine styrene metabolites level was influenced by genotypes of CYP2B6, CYP2D6 and GSTP1 [(280.28 +/- 100.60) mg/g Cr vs (183.48 +/- 127.52) mg/g Cr, (233.04 +/- 77.56) mg/g Cr vs (152.46 +/- 95.47) mg/g Cr, (32.88 +/- 7.14) mg/g Cr vs (24.47 +/- 5.59) mg/g Cr, P < 0.05)]. The metabolism of CYP2B6 G/G homozygotic genotype to styrene was more active than G/T heterozygotic genotype and T/T mutation genotype. The level of PHEMA in GSTP1 homozygotic genotype subjects was significantly higher than that in the group of homozygotic genotype [(32.07 +/- 7.32) mg/g Cr vs (25.59 +/- 6.95) mg/g Cr, P < 0.05)]. The influence of CYP2D6 genotypes on urinary metabolites was also observed in the same study [(56.36 +/- 109.72) mg/g Cr vs (177.13 +/- 116.21) mg/g Cr, (118.73 +/- 84.55) mg/g Cr vs (148.48 +/- 99.83) mg/g Cr, (18.29 +/- 13.50) mg/g Cr vs (19.95 +/- 13.30) mg/g Cr, P < 0.05)].

CONCLUSIONGenotypes of CYP2B6, GSTP1 and CYP2D6 are related to susceptibility to the metabolism of styrene in human.

Adult ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2B6 ; Cytochrome P-450 CYP2D6 ; genetics ; Genotype ; Glutathione S-Transferase pi ; genetics ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Oxidoreductases, N-Demethylating ; genetics ; Polymorphism, Genetic ; Styrene ; adverse effects ; pharmacokinetics ; urine ; Young Adult

This study is to evaluate the cytotoxicity of mitomycin C (MMC) and its analogue 5-(aziridin-1-yl)-3-hydroxymethyl-1-methylindole-4,7-dione (629) as well as the effect of transfection of constitutive androstane receptor (CAR) on their biological effects. HepG2 cells were transfected with the plasmids mCAR1/pCR3 mediated by liposome. Vector pCR3 was used as control. Transfected cells were screened by G418 resistance and limiting dilution. The expressions of plasmid mCAR1/pCR3 and CYP2B6 mRNA were detected by RT-PCR; Cytotoxicities of MMC and 629 in vitro were evaluated in g2car cells and HepG2 cells by MTT method under anaerobic and aerobic conditions. mRNA expression of CAR and CYP2B6 can not be detected in HepG2 cells and HepG2/pCR3 cells but can in g2car cells. It is shown that plasmid mCAR1/pCR3 was transfected into g2car cells successfully and target CYP2B6 was transactivated by CAR. To compare with aerobic and anaerobic, the cytotoxicities of MMC and 629 to HepG2 cells and g2car cells had significantly enhanced (P < 0.05), and transfect CAR gene can improve the cytotoxicity of MMC (P < 0.05), but not 629 (P > 0.05). Furthermore, CYP2B6 is one master enzyme for the metabolism of MMC and not 629. Transfection of CAR can increase expression of CYP2B6 mRNA in HepG2 cells, and can affect cytotoxicities of MMC and 629.
Antibiotics, Antineoplastic ; pharmacology ; Aryl Hydrocarbon Hydroxylases ; biosynthesis ; genetics ; Aziridines ; pharmacology ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Death ; drug effects ; Cell Hypoxia ; Cell Line, Tumor ; Cytochrome P-450 CYP2B6 ; Humans ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Liver Neoplasms ; metabolism ; pathology ; Mitomycin ; pharmacology ; Oxidoreductases, N-Demethylating ; biosynthesis ; genetics ; Plasmids ; RNA, Messenger ; metabolism ; Receptors, Cytoplasmic and Nuclear ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics ; Transfection