Marquee Middle Image

Faculty Profile

Arthur I. Skoultchi, Ph.D.

Dr. Arthur I. Skoultchi

Professor, Department of Cell Biology

Chair, Department of Cell Biology

Judith and Burton P. Resnick Chair in Cell Biology

 

Professional Interests

Our laboratory is interested in understanding the mechanisms controlling mammalian development and cell differentiation.  We study the epigenetic functions of chromatin proteins and transcription factors in control of gene expression in embryonic stem cells, in red blood cells, and in Drosophila. Our approaches involve directed gene inactivation and transgenesis in mice and Drosophila.  We also study control of proliferation and differentiation in red blood cell progenitors and in leukemia cells in which normal development is disrupted.  Currently there are two major projects underway in the lab.

 

Role of H1 Linker Histones and Chromatin Remodeling Factors in Chromatin Structure, DNA Methylation, the Histone Code, Gene Expression and Development in Mice and Drosophila.  Recent studies show that posttranslational modifications of core histones (H2A, H2B, H3, H4) (the Histone Code) play a very important role in control of gene expression.  The H1 linker histones are more diverse than the core histones.  Mice contain 8 H1 histone subtypes including differentiation-specific and tissue-specific subtypes, whereas Drosophila has only one type of H1.  H1’s are thought to be responsible for the final level of packaging DNA into the compact chromatin structure but we know very little about their role in gene expression and development.  We are studying the functional roles of H1 linker histones by inactivating (knocking-out) specific H1 genes in mice and the single H1 in Drosophila.  We are also reintroducing mutant H1 linker histones into H1 depleted mouse cells and flies, to perform structure-function studies.  We have also established a new role for H1 histone in DNA methylation, genomic imprinting and establishment of the histone code.  We are also studying the chromatin remodeling factor that assembles H1 histone into chromatin.

 

Control of Proliferation and Differentiation in Normal and Leukemic Blood Cells: In this project we are investigating how cell proliferation and differentiation are coordinated in normal blood cell development and how this coordination is disrupted in leukemia.  We have investigating the molecular mechanisms for the cross talk between these two cellular programs in normal and leukemic blood cells.  Our studies are focused on the relationships between the master transcription factors that control blood cell development and the cell cycle regulators (cyclins, cyclin-dependent kinases (cdks), cdk inhibitors and RB) that regulate the cell division cycle proliferation.  This project includes genome-wide approaches involving chromatin immunoprecipitation and high throughput sequencing (ChIP-Seq) and gene expression profiling by RNA-Seq.

 

Selected Publications

Lu, X., Wontakal S.N., Kavi H., Kim B.J, Guzzardo P.M., Emelyanov A.V., Xu N., Hannon G.J., Zavadil J. Fyodorov D.V. and A.I. Skoultchi (2013). Drosophila H1 regulates the genetic activity of heterochromatin by recruitment of Su(var)3-9. Science 340(6128): 78-81. PMID: 23559249. [PDF Full Text]

Yang S.M., Kim B.J., Norwood-Toro L., A.I. Skoultchi. (2013) H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation. Proc Natl Acad Sci U S A, 110(5):1708-13 PMID: 23302691. PMCID: PMC3562819. [PDF Full Text]

Yu, Y., Mo Y., Ebenezer D., Bhattacharyya S., Liu H., Sundaravel S., Wonkatal S., Cartier J., Caces B., Artz A., Nischal S., Bhagat T., Bathon D., Maqbool S., Gligich O.,Suzuki M., Steidl U., Godley L., Skoultchi A.I., Greally J., Wickrema A. and Verma A. (2013). High resolution methylome analysis reveals widespread functional hypomethylation during adult human erythropoiesis. J Biol Chem. PMID: 23306203 PMCID: PMC3610956. [ PDF Full Text ]

Popova, E.Y., Grigoryev S..A., Fan Y., Skoultchi A.I., Zhang S.S. and Barnstable C.J. (2013). Developmentally Regulated Linker Histone H1c Promotes Heterochromatin Condensation and Mediates Structural Integrity of Rod Photoreceptors in Mouse Retina. J Biol Chem. PMID: 23645681 PMCID: PMC3682587. [ PDF Full Text ]

Wontakal, S. N., X. Guo, C. Smith, T. MacCarthy, E. H. Bresnick, A. Bergman, M. P. Snyder, S. M. Weissman, D. Zheng and A. I. Skoultchi (2012). A core erythroid transcriptional network is repressed by a master regulator of myelo-lymphoid differentiation. Proc Natl Acad Sci U S A 109(10): 3832-3837. [PDF Full Text ]

Melcer, S., H. Hezroni, E. Rand, M. Nissim-Rafinia, A. I. Skoultchi, C. L. Stewart, M. Bustin and E. Meshorer (2012). "Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation." Nat Commun 3: 910. [PDF Full Text]

Nishiyama, M., A. I. Skoultchi and K. I. Nakayama (2012). "Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-beta-catenin signaling pathway." Mol Cell Biol 32(2): 501-512. [PDF Full Text]

Maclean, J. A., A. Bettegowda, B. J. Kim, C. H. Lou, S. M. Yang, A. Bhardwaj, S. Shanker, Z. Hu, Y. Fan, S. Eckardt, K. J. McLaughlin, A. I. Skoultchi and M. F. Wilkinson (2011). "The rhox homeobox gene cluster is imprinted and selectively targeted for regulation by histone h1 and DNA methylation." Mol Cell Biol 31(6): 1275-1287. [PDF Full Text]

Wontakal SN, Guo X, Will B, Shi M, Raha D, Mahajan MC, Weissman S, Snyder M, Steidl U, Zheng D, Skoultchi AI. (2011). A Large Gene Network in Immature Erythroid Cells Is Controlled by the Myeloid and B Cell Transcriptional Regulator PU.1. PLoS Genet. 2011 Jun;7(6):e1001392. Epub 2011 Jun 9. [PDF Full Text ]

Funato, H., M. Sato, C. M. Sinton, L. Gautron, S. C. Williams, A. Skach, J. K. Elmquist, A. I. Skoultchi and M. Yanagisawa (2010). "Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep." Proc Natl Acad Sci U S A 107(42): 18155-18160. [PDF Full Text]

Eskeland, R., M. Leeb, G. R. Grimes, C. Kress, S. Boyle, D. Sproul, N. Gilbert, Y. Fan, A. I. Skoultchi, A. Wutz and W. A. Bickmore (2010). "Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination." Mol Cell38(3): 452-464. [PDF Full Text]

Papetti, M., Wontakal, S.N., Stopka, T., Skoultchi, A.I. (2010). GATA-1 directly regulates p21 gene expression during erythroid differentiation. Cell Cycle 9(10), 1972-1980. (Epub May 18, 2010). [PDF Full Text]

Burda, P., Curik, N,, Kokavec, J., Basova, P., Mikulenkova, D., Skoultchi, A.I., Zavadil, J., and Stopka, T. (2009). PU.1 Activation Relieves GATA-1-Mediated Repression of Cebpa and Cbfb during Leukemia Differentiation.  Mol Cancer Res. 7, 1693-1703. PMID: 1982599. [PDF Full Text]

Choe, K. S., O. Ujhelly, S. N. Wontakal, and A. I Skoultchi. 2009. PU.1 directly regulates CDK6 gene expression, linking the cell proliferation and differentiation programs in erythroid cells. J. Biol. Chem. Epub December 2, 2009. [PDF Full Text]

Lu, X., SN Wontakal, AV Emelyanov, P. Morcillo, AY Konev, DV Fyodorov, A.I. Skoultchi. 2009. Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure. Genes Dev 23:452-465. PDF Full Text

Nishiyama, M, K., Oshikawa, Y. Tsukada, T. Nakagawa, S Iemura, T. Natsume, Y Fan, A. Kikuchi, A.I. Skoultchi, K.I. Nakayama. 2009. CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. Nat Cell Biol 11:172-82.[PDF Full Text]

Giambra, V., Volpi, S., Emelyanov, A.V., Pflugh, D., Bothwell, A.L., Norio, P., Fan, Y., Ju, Z., Skoultchi, A.I., Hardy, R.R., Frezza, D., Birshtein, B.K. 2008. Pax5 and linker histone H1 coordinate DNA methylation and histone modifications in the 3' regulatory region of the immunoglobulin heavy chain locus. Mol Cell Biol 28, 6123-33.   [PDF Full Text]

Chong, S., Vickaryous, N., Ashe, A., Zamudio, N., Youngson, N., Hemley, S., Stopka, T., Skoultchi, A., Matthews, J., Scott, H.S., de Kretser, D., O'Bryan, M., Blewitt, M., and Whitelaw, E. (2007). Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet 39, 614-622.  [PDF Full Text]

Papetti, M. and Skoultchi, A.I. Reprogramming Leukemia Cells to Terminal Differentiation and Growth Arrest by RNA Interference of PU.1 Molecular Cancer Research 5, 1053-1062, October 1, 2007. doi: 10.1158/1541-7786.MCR-07-0145.  [PDF Full Text ]

Murga M, Jaco I, Fan Y, Soria R, Martinez-Pastor B, Cuadrado M, Yang SM, Blasco MA, Skoultchi AI, Fernandez-Capetillo O. Global chromatin compaction limits the strength of the DNA damage response. J Cell Biol. 2007 Sep 24;178(7):1101-8. [PDF Full Text ]

Woodcock, C.L., A.I. Skoultchi and Y. Fan (2006). Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res 14:17-25.  [PDF Full Text ]

Lang, D., Lu, M.M., Huang, L., Engleka, K.A., Zhang, M., Chu, E.Y., Lipner, S., Skoultchi, A., Millar, S.E., and Epstein, J.A. (2005). Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433, 884-887.   [PDF Full Text ]

Fan, Y., T. Nikitina, J. Zhao, T. Fleury, R. Bhattacharyya, E. Bouhassira, A. Stein, C. Woodcock and A.I. Skoultchi (2005). Depletion of histone H1 in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell 123(7): 1199-1212  [PDF Full Text ]

Stopka, T., D. Amanatullah, M. Papetti and A.I. Skoultchi (2005). “PU.1 inhibits the erythroid program by binding to GATA-1 on DNA and creating a repressive chromatin structure.?nbsp; Embo J., 24(21): 3712-23  [PDF Full Text ]

Yu, Y.L., Chiang, Y.J., Chen, Y.C., Papetti, M., Juo, C.G., Skoultchi, A.I., and Yen, J.J. (2005). MAPK-mediated phosphorylation of GATA-1 promotes Bcl-XL expression and cell survival. J Biol Chem 280, 29533-29542. PMID: 15967790 [PDF Full Text ]

Fan Y. and Skoultchi AI. (2004) Genetic Analysis of H1 Linker Histone Subtypes And Their Functions In Mice. Methods Enzymol. 377:85-107.  [PDF Full Text ]

Choe K.S., F. Radparvar, et al. (2003). “Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1. Cancer Res 63(19): 6363-9  [PDF Full Text ]

Rekhtman N., K.S. Choe, et al. (2003) “PU.1 and pRB interact and cooperate to repress GATA-1 and block erythroid differentiation. Mol Cell Biol. 23(21): 7460-74  [PDF Full Text ]
 

 

More Information About Dr. Arthur Skoultchi

Cell Biology

Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.

Contact

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Chanin Building, Room 402
Bronx, NY 10461

Tel: 718.430.2169
Fax: 718.430.8574
arthur.skoultchi@einstein.yu.edu

 
Collexis Research Profiles
Einstein Research Profiles (ERP) is one of the innovative technologies to create collaborative bridges within and across the entire bench-to-bedside-to-population spectrum of research. The ERP website has been developed in partnership with Collexis to give investigators easy access to PubMed publications, coauthor networks, information about NIH grants, and research networks.