Feng XU

Adipocyte Biology and Epigenetics


Feng XU
Lab Location: #7-16   Email: fxu@imcb.a-star.edu.sg   Tel: 65869678

Dr. Feng Xu has been a principal investigator in the Agency for Science, Technology and Research (A*STAR) since 2009, first at SICS and now at IMCB. He was trained as a chromatin biologist at the University of California, Los Angeles before establishing his lab in Singapore. His current research interest centers on the epigenetic regulation of energy balance. This topic includes the study of microRNAs, post-translational modifications on histones and non-histone metabolic regulators in the maintenance of metabolic homeostasis. His lab utilizes both advanced genomic tools as well as classic biochemistry and molecular biology techniques to tackle the scientific questions of interest. In addition, he is also interested in developing novel therapeutic approaches in treating metabolic disorders such as obesity and diabetes.


Epigenetic Regulation of Metabolic Homeostasis

Obesity and its related diseases such as diabetes increasingly are responsible for significant economic and social burdens in established and emerging countries. For instance, diabetes alone, is affecting more than 170 million people worldwide. As such, understanding the molecular mechanism that controls adipose (fat) cell differentiation would greatly enhance our ability to solve these problems. Adipogenesis is a complex physiological process that requires concerted regulation of gene expression by various adipogenic factors. Among these regulators are many histone modifying enzymes and chromatin remodelers, suggesting that epigenetic mechanisms play essential roles in modulating adipogenesis. In addition to histone modifications, microRNA represents another major group of epigenetic regulators involved in diverse physiological processes including adipogenesis. Our current research centers on the function of histone modifications and microRNAs in white adipocyte differentiation. And we are extending our research to the epigenetic control of brown adipocyte differentiation as well as lineage commitment from multipotent stem cells. To fully decipher the epigenetic mechanisms controlling adipogenesis and lineage commitment, we utilize the advanced genomic and proteomic methodologies as well as classic biochemistry and molecular biology techniques in our studies. Besides our basic research into the molecular mechanism of adipogenesis, we are also interested in identifying novel drug targets to treat obesity and metabolic diseases such as diabetes.



Recent Publications

Ng, R., Hussain, N.A., Zhang, Q.Y., Chang, C.W., Li, H.Y., Han, W.P., Stunkel, W. and Xu, F.* (2017)
miRNA-32 drives brown fat thermogenesis and trans-activates subcutaneous white fat browning in mice.
Cell Reports. 19, 1229–1246.

Julien, S.G., Kim, S.Y., Brunmeir, R., Sinnakannu, J.R., Ge, X.J., Ma, W., Yaligar, J., KN, B.P., Velan, S.S., Röder, P.V., Zhang, Q.Y., Sim, C.K., Wu, J.Y., Xie, W., McFarlane, C., Han, W.P. and Xu, F.* (2017)
Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle.
PLoS Biology. 16;15(2):e1002597. (Research Highlights by Nature Reviews Endocrinology)

Brunmeir, R., Wu, J.Y., Peng, X., Julien, S.G., Zhang, Q.Y., Xie, W.* and Xu, F.* (2016)
Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators of Murine Brown Adipogenesis.
PLoS Genetics. 12(12):e1006474.

Sim, C.K. #, Kim, S.Y. #, Brunmeir, R., Zhang, Q.Y., Li, H.Y., Dharmasegaran, D., Leong, C., Lim, Y.Y., Han, W.P. and Xu, F.* (2017) Regulation of White and Brown Adipocyte Differentiation by RhoGAP Dlc1.
PLoS One. 12(3):e0174761.

Li, N., Zhou, Z.S., Shen, Y., Xu, J., Miao, H.H., Xiong, Y., Xu, F., Li, B.L., Luo, J. and Song, B.L.* (2016)
Inhibition of the SREBP pathway suppresses hepatocellular carcinoma through repressing inflammation.
Hepatology. 2016 Dec 27.

Kim, S.Y. #, Sim, C.K. #, Zhang, Q.Y., Tang, H., Brunmeir, R., Pan. H., Karnani, N., Han, W.P., Zhang, K.L.* and Xu, F. * (2016)
An Alternative Strategy for Pan-acetyl- lysine Antibody Generation.
PLoS One. 11(9):e0162528.

Zheng H, Huang B, Zhang B, Xiang Y, Du Z, Xu Q, Li Y, Wang Q, Ma, J., Peng, X., Xu, F. and Xie, W.* (2016)
Resetting Epigenetic Memory by Reprogramming of Histone Modifications in Mammals.
Molecular Cell. 63(6):1066-79.

Zhang, B., Zheng, H., Huang, B., Li, W., Xiang, Y., Peng, X., Ming, J., Wu, X., Zhang, Y., Xu, Q., Liu, W., Kou, X., Zhao, Y., He, W., Li, C., Chen, B., Li, Y., Wang, Q., Ma, J., Yin, Q., Kee, K., Meng, A., Gao, S., Xu, F., Na, J., and Xie, W.* (2016)
Allelic reprogramming of the histone modification H3K4me3 in early mammalian development.
Nature. 537(7621):553-557.

Wu. J., Huang, B., Chen. H., Yin, Q.Z., Li, W.Z., Liu. Y., Xiang, Y.L., Zhang. B.J., Zheng, H., Xia. W.K., Ming, J., Li, Y.Y., Zhang. W.H., Wang, Q.J., Zhang, J., Peng, X., Tian, G., Xu, F., Chang, Z., Yang, X.R., Na, J., and Xie, W.* (2016)
The landscape of accessible chromatin in mammalian preimplantation embryos.
Nature. 534(7609): 652-7.   

Sundaram, A., Hughes, T., Biondi, S., Bolduc, N., Bowman, S.K., Camilli, A., Chew, Y.C., Couture, C., Farmer, A., Jerome, J.P., Lazinski, D.W., McUsic, A., Peng, X., Shazand, K., Xu, F., Lyle, R.* and Gilfillan, G.D.* (2016)
A comparative study of ChIP-seq library preparation methods.
BMC Genomics. 17(1):816.

Kim, S.Y. #, Sim, C.K. #, Tang, H., Han, W.P., Zhang, K.L.* and Xu, F. * (2016) Acetylome study in mouse adipocytes identifies targets of SIRT1 deacetylation in chromatin organization and RNA processing.
Arch Biochem Biophys. 598:1-10.

Kim, S.Y. #, Sim, C.K. #, Tang, H., Han, W.P., Zhang, K.L.* and Xu, F. * (2015) Acetylome Analysis Identifies SIRT1 Targets in mRNA-processing and Chromatin- remodeling in Mouse Liver.
PLoS One. 10(10):e0140619.

Kim, S.Y., Zhang, Q.Y., Brunmeir, R., Han, W.P. and Xu, F. * (2015)
SIRT1 Interacts with and Deacetylates ATP6V1B2 in Mature Adipocytes.
PLoS One. 10(7):e0133448.

Joseph, R., Poschmann, J., Sukarieh, R., Too, P.G., Julien, S.G., Xu, F., Teh, A.L., Holbrook, J.D, Ng, K.L., Chong, Y.S., Gluckman, P.D., Prabhakar. S. and Stünkel, W.* (2015)
Acyl-CoA synthetase 1 in differentiated adipocytes from small for gestational age neonates: Putative association with fetal programming of cellular insulin sensitivity and lipid content.
Mol Endocrinol
. 29(6):909-920.

Peng, X., Wu, J.Y., Brunmeir, R., Kim, S.Y., Zhang, Q.Y., Ding, C.M., Han, W.P., Xie, W. and Xu, F. * (2015)
TELP, a sensitive and versatile library construction method for next-generation sequencing.
Nucleic Acids Res. 43(6):e35.

Nicholas, D., Tang, H., Zhang, Q.Y., Xu, F., Langridge, W. and Zhang, K.L.* (2015) Protein profiling reveals dynamic H1 expression and histone modifications during human monocyte differentiation.
Molecular and Cellular Proteomics. 14(1):15-29.

Yang, W.L., Thein, S., Lim, C.Y., Ericksen, R.E., Sugii, S., Xu, F., Robinson, R., Kim, J.B. and Han, W.P.* (2014)
Arp2/3 complex regulates adipogenesis by controlling cortical actin remodeling.
 Biochemical Journal. 464(2), 179-192.

Ramlee, M.K., Zhang, Q.Z., Idris, M., Peng, X., Sim, C.K., Han, W.P. and Xu, F. * (2014)
Histone H3 K27 acetylation marks a potent enhancer for the adipogenic master regulator gene Pparg2.
Cell Cycle. 13(21), 3414-3422.

Gao, M., Sim, C.K., Leung, C., Hu, Q.L., Feng, G.X., Xu, F.* Tang, B.Z.* and Liu, B.* (2014)
A fluorescent light-up probe for specific mitochondrial imaging to identify differentiating brown adipose cells.
Chemical Communications. 50(61), 8312-8315.

Yang, W.L., Thein, S., Wang, X.R., Bi, X.Z., Ericksen, R.E., Xu, F., and Han, W.P.* (2014) BSCL2 / seipin regulates adipogenesis through actin cytoskeleton remodeling.
Human Molecular Genetics. 23(2), 502-513.

Yang, W.L., Thein, S., Guo, X.X., Xu, F., Venkatesh, B., Sugii, S., Radda, G.K., and Han, W.P.* (2013)
Seipin differentially regulates lipogenesis and adipogenesis through a conserved core sequence and an evolutionarily acquired C-terminus.
Biochemical Journal. 452, 37-44.

Villanueva, C.J., Vergnes, L., Drew, B., Tu, Y.P., Hu, Y., Peng, X., Xu, F., Saez, E., Wroblewski, K., Hevener, A., Reue, K., Fong, L.G., Young, S.G. and Tontonoz, P.* (2013)
Adipose subtype-selective recruitment of TLE3 or Prdm16 by PPARg specifies lipid storage versus thermogenic gene programs.
Cell Metabolism. 17, 423–435.

Yang, W.L., Guo, X.X., Thein, S., Xu, F., Sugii, S., Baas, P.B., Radda, G.K., and Han, W.P.* (2013)
Regulation of adipogenesis by katanin-mediated cytoskeleton remodeling is facilitated by MEC-17-dependent acetylation of a-tubulin.
Biochemical Journal. 449, 605–612.

Zhang, Q.Y., Ramlee, M.K., Brunmeir, R., Villanueva, C.J., Halperin, D. and    Xu, F.* (2012)
Dynamic and distinct histone modifications modulate the expression of key adipogenesis regulatory genes.
Cell Cycle 11:23, 4310–4322.

Sun, W., Xie, W., Xu, F., Grunstein, M. and Li, K.C. (2009)
Dissecting nucleosome free regions by a segmental semi-Markov model.
PLoS One. 4(3):e4721.

Xie, W., Song, C., Young, N.L., Sperling, A.S., Xu, F., Sridharan, R., Conway, A.E., Garcia, B.A., Plath, K., Clark, A.T. and Grunstein, M. (2009)
Histone H3 lysine 56 acetylation is linked to the core transcriptional network in human embryonic stem cells.
Molecular Cell. 33, 417-427.

Xu, F., Zhang, Q.Y., Zhang, K.L., Xie, W. and Grunstein, M. (2007) Sir2 Deacetylates Histone H3 Lysine 56 to Regulate Telomeric Heterochromatin Structure in Yeast.
Molecular Cell. 27, 890-900.

Millar, C.B., Xu, F., Zhang, K.L. and Grunstein, M. (2006)
Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeast.
Genes & Development. 20 (6), 711-722.

Xu, F., Zhang, K.L. and Grunstein, M. (2005)
Acetylation in Histone H3 Globular Domain Regulates Gene Expression in Yeast.
Cell. 121,375-385.

Yu, Y., Liu, Y., Shen, N., Xu, X., Xu, F., Jia, J., Jin, Y., Arnold, E. and Ding, J. (2004) Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment: insights into substrate recognition, tRNA binding, and angiogenesis activity.
J Biol Chem. 279(9), 8378-8388.

Wang, Z.C., Wang, X.M., Jin, Y.X., Jiao, B.H., Xu, F., Miao, M.Y. and Zhu, K.J. Search for difference in aminoacylation of mitochondrial DNA-encoded wild-type and mutant human tRNALeu (UUR). (2003)
. 55(3), 139-144.

Xu, F., Jiang, G., Li, W., He, X., Jin, Y.X. and Wang, D. (2002)
Three G.C base pairs required for the efficient aminoacylation of tRNATrp by tryptophanyl-tRNA synthetase from Bacillus subtilis.
Biochemistry. 41(25), 8087-8092.

Jia, J., Xu, F., Chen, X., Chen, L., Jin, Y.X. and Wang, D.B. (2002)
Two essential regions for tRNA recognition in Bacillus subtilis tryptophanyl-tRNA synthetase.
Biochem J. 365(Pt 3), 749-756.

Xu, F., Chen, X.L., Xin, L., Chen, L., Jin, Y.X. and Wang, D.B. (2001)
Species- Specific Differences in the Operational RNA Code for Aminoacylation of tRNATrp.
Nucleic Acids Res. 29, 4125-4133.

Xu, F., Jia, J., Jin, Y.X. and Wang, D.B. (2001)
High-Level expression and single- step purification of human tryptophanyl-tRNA synthetase.
Protein Express. Purif. 23, 296-300.

Xu, R.H., Liu, J., Chen, X.W., Xu, F., Xie, Q., Yu, H., Guo, Q., Zhou, X.Q. and Jin, Y.X. (2001)
Ribozyme-mediated Inhibition of Caspase-3 Activity Reduces Apoptosis Induced by 6-Hydroxydopamine in PC12 Cells.
Brain Research. 899, 10-19.