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| 1 | Tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine(5hmC)显示文摘As a dioxygenase, Ten-Eleven Translocation 2(TET2) catalyzes subsequent steps of 5-methylcytosine(5 mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation,and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells(macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2^(-/-) mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine(5 hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5 hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities. | Yajing Chu Zhigang Zhao David Wayne Sant Ganqian Zhu Sarah M. Greenblatt Lin Liu Jinhuan Wang Zeng Cao Jeanette Cheng Tho Shi Chen Xiaochen Liu Peng Zhang Jaroslaw P. Maciejewski Stephen Nimer Gaofeng Wang Weiping Yuan Feng-Chun Yang Mingjiang Xu | 2018 | Genomics, Proteomics & Bioinformatics2018，16，3： | 2 |
| 2 | H3K36 methyltransferase NSD1 regulates chondrocyte differentiation for skeletal development and fracture repair显示文摘Chondrocyte differentiation is a critical process for endochondral ossification,which is responsible for long bone development and fracture repair.Considerable progress has been made in understanding the transcriptional control of chondrocyte differentiation;however,epigenetic regulation of chondrocyte differentiation remains to be further studied.NSD1 is a H3K36(histone H3 at lysine 36)methyltransferase.Here,we showed that mice with Nsd1 deficiency in Prx1+mesenchymal progenitors but not in Col2+chondrocytes showed impaired skeletal growth and fracture healing accompanied by decreased chondrogenic differentiation.Via combined RNA sequencing(RNA-seq)and chromatin immunoprecipitation sequencing(ChIP-seq)analysis,we identified sex determining region Y box 9(Sox9),the key transcription factor of chondrogenic differentiation,as a functional target gene of NSD1.Mechanistically,NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region,constituting a novel epigenetic regulatory mechanism of chondrogenesis.Moreover,we found that NSD1 can directly activate the expression of hypoxia-inducible factor 1α(HIF1α),which plays a vital role in chondrogenic differentiation through its regulation of Sox9 expression.Collectively,the results of our study reveal crucial roles of NSD1 in regulating chondrogenic differentiation,skeletal growth,and fracture repair and expand our understanding of the function of epigenetic regulation in chondrogenesis and skeletal biology. | Rui Shao Zhong Zhang Zhan Xu Huiling Ouyang Lijun Wang Hongwei Ouyang Matthew Greenblatt Xi Chen Weiguo Zou | 2021 | Bone Research2021，9，3： | 2 |
| 3 | Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection显示文摘 | Kobayashi A Greenblatt RM Anastos K | 2004 | Cancer Res2004，64，18： | 1 |
| 4 | Human drug metabolism and the cytochromes P450 application and relevance of in viro models显示文摘 | Venkatakrishnan K Von ML Greenblatt DJ | 2001 | J Clin Pharmacol2001，41，11： | 1 |
| 5 | Sex differences in pharmacokinetics and pharmacodynamics显示文摘 | GANDHI M AWEEKA F GREENBLATT R M | 2004 | Annu Rev Pharmacol Toxicol2004，44，： | 1 |
| 6 | Calcineurin regulates innate antifungal immunity in neutrophils显示文摘 | Greenblatt MB Aliprantis A Hu B | 2010 | J Exp Med2010，207，5： | 1 |
| 7 | Escitalopram (Scitalopram) and its metabolites invitro:cytochromes mediating biotransformation,inhibitory effects,and comparison to R-citalopram显示文摘 | Von Moltke LL Greenblatt DJ Giancarlo GM | 2001 | Drug Metab Dispos2001，29，： | 1 |
| 8 | Effects of the antifungal agents on oxidative drug metabolism:clinical relevance显示文摘 | Venkatakrishnan K von Moltke LL Greenblatt DJ | 2000 | Clin Pharmacokinet2000，38，2： | 1 |
| 9 | Derlin-1 is a rhomboid pseudo-protease required for the dislocation of mutant a-1 antitrypsin from theendoplasmic reticulum显示文摘 | Greenblatt EJ Olzmann JA Kopito RR | 2011 | Nat Struct Mol Biol2011，18，10： | 1 |
| 10 | Mutations in the p53 tumor suppressor gene:clues to cancer etiology and molecular pathogenesis显示文摘 | Greenblatt M S Benntt W P Hollstein M | | 0，，18： | 1 |
| 11 | Database of p53 gene somatic mutations in human tumours and cell lines显示文摘 | Hollstein M Rice K Greenblatt M S | 1994 | Nucleic Acids Res1994，22，1： | 1 |
| 12 | Type of stimulation protocol affects oocytes maturity, and cleavage rate after intracytoplasmic sperm injection显示文摘 | Greenblatt EM Meriano JS Casper RF | 1995 | Fertil steril1995，64，： | 1 |
| 13 | Importance of protein binding for the interpretation of serum or plasma drug concentrations显示文摘 | Greenblatt DJ Sellers EM Koch-Weser J | 1982 | J Clin Pharmacol1982，22，： | 1 |
| 14 | Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection显示文摘 | KOBAYASHI A GREENBLATT R M ANASTOS K | 2004 | Cancer Res2004，64，18： | 1 |
| 15 | Preoperative factors predict perioperative morbidity and mortality after pancreaticoduodenectomy显示文摘 | Greenblatt DY Kelly KJ Rajamanickam V | 2011 | Ann Surg Oncol2011，18，8： | 1 |
| 16 | Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection显示文摘 | Kobayashi A Greenblatt RM Anastos K el al | 2004 | Cancer Res2004，64，18： | 1 |
| 17 | Gross cystic dis-ease of the breast显示文摘 | Greenblatt RB Mahesh VB Sullivan D | 1987 | Maturitas1987，9，2： | 1 |
| 18 | Direct interaction of the hepatitis B virus HBx protein with p53 leads to inhibition by HBx of p53 response element-directed transactivation显示文摘 | Truant R Antunovic J Greenblatt J | 1995 | J Virol1995，69，3： | 1 |
| 19 | Structural insights into substrate traffic and inhibition in acetylcholinesterase 显示文摘 | Colletier JP Fournier D Greenblatt HM | 2006 | EMBO J2006，25，： | 1 |
| 20 | Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects显示文摘 | Smithline HA Donnino M Greenblatt DJ | 2012 | BMC Clin Pharmacol2012，12，： | 1 |
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