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Shi Laboratory Recent Publications

Original Articles - Selected from 114 publications

Shi, Y*.and Mello, C. (1998).  A CBP/p300 homolog specifies multiple differentiation pathways in C. elegans.  Genes & Dev.  Vol 12, 943-955. (Cover Photo).  Commented in: Trends in Genetics 14: 183, 1998; Nature Biotechnology 16:405, 1998. Read on PubMed | PDF  

*Corresponding author

This paper used the then nascent RNAi technology to identify the biological role of the histone acetyltransferase CBP in development and to demonstrate the antagonistic relationship between CBP and HDAC in regulating endoderm differentiation.

Calvo, D., Victor, M., Sui, G-C., Luck, M. P-S., Wen, G-Y., Dufourcq, P., Maduro, M., Rothman, J. and Shi, Y. (2001).  A POP-1 repressor complex restricts cell type specific gene transcription during Caenorhabditis elegans early embryogenesis. EMBO J, Vol 20: 7197- 7208. Read on PubMed | PDF

This paper describes a molecular mechanism by which POP-1 represses transcription of cell type-specific genes important for cell fate determination during C. elegans early embryogenesis.

Sui, G.C., Soohoo, C, Affar, E.B., Shi, Y.J., Forrester, W., and Shi, Y. (2002). A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc. Natl. Acad. Sci. USA.  Vol 99:5515-20.    Read on PubMedPDF

This paper was one of the first to describe the DNA-vector based RNAi approach.

Shi, YJ., Sawada, J-I., Sui, G.C., Affar, E.B., Whetstine, J., Lan, F., Ogawa, H., Luke, M.,P-S., Nakatani, Y.,and Shi, Y. (2003). Coordinated histone modifications mediated by a CtBP co-repressor complex.  Nature Vol 422:735-8. Read on PubMed | PDF

This paper describes the CtBP super-complex, which includes the CoREST and CDYL sub-complexes, both of which can be recruited by REST for repression. The paper shows that establishment of a repressive environment requires a series of coordinated histone modifications.

Shi, YJ., Lan, F., Matson, C., Mulligan, P., Whetstine, JR., Cole, PA., Casero, RA. and Shi, Y. (2004).  Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell  Vol 119:941-953.  (Commented in Cell Vol 119:903-906, Science (2004) Vol 306:2171, Nature (2005) Vol 433:29, Cell 2005, Vol 122:654-658, Faculty 1000 All Time Top 10). Read on PubMed | PDF

This paper describes the identification of the first histone demethylase LSD1, which is a component of the REST-CoREST  repressor complex.

Shi, YJ, Matson, C., Lan, F., Iwase, S., Baba, T. and Shi, Y. (2005). Regulation of LSD1 histone demethylase activity by its associated factors.  Mol Cell Vol 19:857-864.  (Commented in Cell 2005, Vol 122:654-658).  Read on PubMed | PDF

This paper describes regulation of LSD1 activity in vivo and the biochemical and functional interactions with histone deacetylases and CoREST, both of which are components of the CoREST co-repressor complex.

Whetstine, JR., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G.,Colaiacovo, M., and Shi, Y. (2006). Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell Vol 125:467-81. (Commented in Research Highlight, Nat. Rev. Mol. Cell. Biol. June, 2006) Read on PubMed | PDF

This paper describes the identification of the first family of demethylases that remove trimethyl groups on histones.

Chen, Z., Zhang, J., Whetstine, JR., Hong X.,  Davrazou, F., Kutateladze, TG., Simpson, M., Mao, Q., Pan, CH., Dai, S., Hagman, J., Hansen, K., Shi, Y., and Zhang, G. (2006) Structural insights into histone demethylation by the JMJD2 family members.  Cell Vol 125:703-717. Read on PubMed | PDF

This paper describes the first crystal structure of the catalytic domain of the JmjC -type histone demethylases.

Lan, F., Zaratiegui, M., Villen, J., Vaughn, M., Verdel, A., Gygi, S., Moazed, D., Martienssen, R. and Shi, Y. (2007). S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatin gene transcription.  Mol Cell Vol 16: 89-101. (Mol Cell Preview, Vol 26:160-62). Read on PubMed | PDF 

This paper describes the in vivo molecular mechanism and function of LSD1 homologs in S. pombe.

Iwase, S, Lan, F., Bayliss, P., de la Torre-Ubieta, L., Qi, H., Huarte, M., Whetstine, JR.,Bonni, A., Roberts, T., and Shi, Y. (2007). The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell, 128:1077-88. Read on PubMed | PDF

This paper describes the identification of a small family of demethylases specific for H3K4me3/2, and identifies a link between histone demethylation and mental retardation.

Lan, F., Collins, R., De Cegli, R., Alpatov, R., Horton, J.R., Shi, XB, Gozani, R., Cheng, XD, and Shi, Y. (2007). Recognition of unmethylated H3K4 links BHC80 to LSD1 mediated gene repression. Nature, Vol 448:718-723. Read on PubMed | PDF

This paper describes the identification of the first protein module that recognizes the unmethylated state of histone H3K4, which has been proposed to play a potential role in directing DNA methylation.

Lan, F., Bayliss, PE., Rinn, J., Whetstine JR., Wang JK., Chen, SZ., Iwase, S., Roberts,TM., Chang, HY., and Shi, Y. (2007). A histone H3 lysine 27 demethylase regulates animal posterior development. Nature Vol 449:689-94. (Commented by Swigut, T. and Wysocka, J. (2007) “H3K27 demethylases, at long last” Cell Vol 131:29-32.) Read on PubMed | PDF

This paper describes the identification of a subfamily of enzymes that demethylate H3K27me3, a modification important for regulation of developmental genes, which was thought to be stable and irreversible even after the identification of demethylases that reverse methylation at other histonelysine residues.

Liu, HF, Schmidt-Supprian, M., Shi, YJ., Hobeika, E., Barteneva, N., Humaa, H., Pelanda,R., Reth, M., Skok, J.,Rajewsky, K., and Shi, Y. (2007). Yin Yang 1 is a critical regulator of B-cell development. Genes & Dev, Vol 21:1179-89). PDF (Perspective by K. Calame and M. Atchison (2007) YY1 helps to bring loose ends together, Genes & Dev. Vol 21:1145-52).

            This paper describes a novel and unique role of YY1 in regulating pro-B cell differentiation, possibly by regulating IgH locus contraction.

Mulligan, P., Westbrook, T.F., Ottinger, Macia, E., Liu, JS., Shi, YJ., Barretina, J., Howley, P.M., Elledge, S.J., and Shi, Y. (2008). CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation.  Mol Cell, Vol 32(5): 718-26. PDF (Featured Article, highlighted by Cell Vol 135 (2008) Leading Edge p981).

            This paper describes a potential tumor suppressor role for CDYL, which is a nuclear homolog of enoyl CoA hydratases involved in fat metabolism, and a component of the CtBP super-complex.

Qi, HH*, Sarkissian, M.*, Hu, GQ., Wang Z., Bhattacharjee, A., Gordon, DB., Gonzales, M., Lan, F., Ongushaha, PP., Huarte, M., Yaghi, NK., Lim, S., Garcia B., Brizuela, L., Zhao, KJ., Roberts, TM+, and Shi, Y+. (2010). Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature, Vol 466:503-7. PDF

*Equal contribution.

+Corresponding authors

            This paper identifies the first demethylase that has an activity towards histone H4K20me1. Consistent with its documented role in human X-linked mental retardation and craniofacial development, this study identified a role for PHF8 in zebrafish neuronal and craniofacial development and provided a potential underlying molecular mechanism that links PHF8 to the regulation of TGFbeta signaling pathway.

Reviews, Book Chapters and Editorials

Shi, Y. Lee, J.-S., and Galvin, K.M. (1997)  Everything you have ever wanted to know about Yin Yang 1......    BBA Reviews on Cancer.  1332: F25-F48.

Johnstone R, W. and Shi, Y. (2002). The Wilms Tumor Suppressor WT1: one gene, many proteins and functions?  Encyclopedia of Cancer (2nd edition).  Edited by Bertino et al. P. 543-551.  Academic Press, San Diego.

Shi, Y.(2003).  Mammalian RNAi for the masses.  Trends in Genetics.  Vol 19: 9-12 (#1 downloaded article among all of Elsevier publications in 2003).

Wall, N. and Shi, Y.  (2003).  The power of small RNA: can RNA interference be effectively exploited for therapy?  The Lancet.  Vol 362: 1401-3.

Shi, Y*and Blackwell, T. K. (2003).  A two-tiered transcription regulation mechanism that protects germline identity: lessons from the worms.  Mol Cell. Vol 12:1062-64.

*Corresponding author.

Shi, YJ and Shi, Y.  (2004).  Metabolic enzymes in transcription-a direct link between

metabolism and regulated gene expression?  Trends in Genetics, Vol 20:445-52.

Liu, HF and Shi, Y. (2005).  Yin Yang 1 “Zinc Finger Proteins: from Atomic Contact to Cellular Function.”  pp 182-193.  (Edited by Shiro Iuchi and Natalie Kuldell), Landers Biosciences and Kluwer Academic Press. 

Sui, GC and Shi, Y,.(2005). Gene silencing by a DNA vector-based RNAi technology.

Methods in Mol. Biol. Vol 309:205-218 (edited by Gordon Carmichael) Humana Press. 

Shi, YJ and Shi, Y. (2006). CtBP co-repressor complex: A multi-enzyme machinery that

coordinates chromatin modifications. pp77-80, CtBP Family of Proteins (edited by G. Chinnadurai).  Landers Biosciences. 

Shi, Y*and Whetstine, J.  (2007). Dynamic regulation of histone lysine methylation by    demethylases.  Mol. Cell, Vol 25:1-14.  *Corresponding author.

Shi, Y. (2007).  Taking epigenetics center stage. Cell Vol 128: 639-40.

Shi, Y. (2007). Histone demethylases: emerging roles in development, physiology and disease. Nat. Rev. Genet.  Vol 8:829-33.

Shi, Y. (2007). "Histone Modification and Transcriptional Repression", in Carey, M. and Smale, S. (eds), Eukaryotic Gene Regulation: From Chromatin to Transcription to mRNA Processing, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London. LINK

Allis, C.D., Berger, S.L., Cote, J., Dent, S., Jenuwien T., Kouzarides, T., Pilius, L., Reinberg, D. Shi, Y., Shiekhattar, R., Shilatifard, A., Workman, J., Zhang, Y. (2007) New nomenclature for chromatin-modifying enzymes. Cell, Vol 131: 633-636.

Lan, F., Nottke, A.C., and Shi, Y. (2008). Mechanisms involved in the regulation of histone lysine demethylases.  Curr. Opin. Cell Biol. Vol 20:316-325.

Nottke, A.C., Colaiacovo, M., and Shi, Y. (2009). Developmental roles for the histone lysine demethylases. Development. Vol 136(6):879-89.

Lan, F. and Shi, Y. (2009). Epigenetic regulation: methylation of histones and non-histone proteins.  Sci China C Life Sci Vol 52:311-22.

Mosammaparast, N., and Shi, Y. (2010). Reversal of histone methylation: Biochemical and molecular mechanisms of histone demethylases.  Ann. Rev. Biochem. Vol 79:155-79.

Iwase, S., and Shi, Y. (2011) Histone and DNA modifications in mental retardation. Prog. Drug Res. Vol 67: 147-73. Review.

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