Faculty Profile
Arthur I. Skoultchi, Ph.D.
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. Our approach is to investigate systems in which these processes are disturbed, either by malignant transformation (leukemia) or by directed gene inactivation in mice and Drosophila. Currently there are three major projects underway in the lab.
Molecular Mechanisms of Leukemia: In this project we are investigating the molecular mechanisms for a block to differentiation present in blood cell tumors (leukemias). We have traced the cause of the differentiation block to a transcription factor called PU.1. We are trying to learn how dysregulation of PU.1 expression causes the leukemia cells to stop differentiating and start proliferating in an uncontrolled manner by studying the effect of PU.1 on other gene products, including, other transcription factors like GATA-1 and co-factors like RB that promote differentiation, and cyclins, cyclin-dependent kinases (cdks) and cdk inhibitors that promote proliferation. This project includes genome-wide approaches involving chromatin immunoprecipitation and high throughput sequencing (ChIP-Seq) and gene expression profiling with microarrays.
Role of H1 Linker Histones and Chromatin Remodeling Factors in Chromatin Structure, DNA Methylation, 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 connection between H1 histones, DNA methylation and genomic imprinting and we are learning how H1 regulates DNA methylation. We also have a new knock-out mouse for the SNF2H chromatin remolding ATPase, which assembles H1 histone into chromatin.
Human ES Cell Proliferation and Totipotency: Continuous cell proliferation is required to maintain human embryonic stem cell totipotency. We have found that certain central regulators of the cell cycle also control differentiation decisions in the hematopoietic system. We are investigating which cell cycle regulators control human ES cell proliferation and whether these molecules also control their totipotency
Selected Publications
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
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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
Education
- Graduate Medical Education (G.M.E.)
- Graduate Program (Ph.D.)
- Master in Bioethics (M.S.)
- Masters in Clinical Research (M.S.)
- Master of Public Health (M.P.H.)
- Medical Program (M.D.)
- MSTP Program (M.D. - Ph.D.)
Einstein Senate
College of Medicine
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