Biology

Yuhong Fan, Assistant Professor

Ph.D., Cell Biology, Albert Einstein College of Medicine

Phone: 404-385-1312
Fax: 404-894-0519
Office: (IBB) 2313/2228 (lab)

Research Interests

Epigenetics, Chromatin, Gene Expression, Function of Linker Histones in Mammalian Development and Stem Cell Differentiation

Current Research

Epigenetic mechanisms are crucial for chromatin structure reprogramming and gene expression during mammalian development and cell differentiation. Dysregulation of epigenetic information is implicated in many human diseases including cancer because it disrupts fundamental processes such as imprinting, X chromosome inactivation, and tissue specific and developmental gene regulation. H1 linker histones are major chromatin structural proteins that associate with nucleosome core particles and play a key role in mediating higher order chromatin structure folding. Previously we showed, by inactivating 3 H1 linker histone genes simultaneously, that the total amount of H1 is essential for mammalian development. We derived triple H1 null embryonic stem cell lines and showed that H1 is particularly important in controlling several imprinted gene expression in these cells. These studies suggested a new link between H1 and DNA methylation. Using genetic modified mouse models and stem cell culture system, we seek to further elucidate the mechanisms of the multiple levels of epigenetic regulations that are required for establishing and maintaining tissue and cell type specific functions.

Lab
positions available

Selected Publications

Nishiyama M, Oshikawa K, Tsukada Y, Nakagawa T, Iemura S, Natsume T, Fan Y, Kikuchi A, Skoultchi AI, Nakayama KI. (2009) CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. Nat Cell Biol. 11(2):172-82.

Oyelere AK, Chen PC, Guerrant W, Mwakwari SC, Hood R, Zhang Y, Fan Y. (2009) Non-peptide macrocyclic histone deacetylase inhibitors. J Med Chem.52(2):456-68.

Giambra V, Volpi S, Emelyanov AV, Pflugh D, Bothwell AL, Norio P, Fan Y, Ju Z, Skoultchi AI, Hardy RR, Frezza D, Birshtein BK. (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(19):6123-33.

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

Woodcock C.L., Skoultchi A.I. and Fan Y. (2006)  Role of Linker Histone in Chromatin Structure and Function: H1 Stoichiometry and Nucleosome Repeat Length.  Chromosome Research 14(1):17-25. <PDF>.

Fan Y., Nikitina T., Zhao J. ,  Fleury T.J., Bhattacharyya R., Bouhassira E.E., Stein A., Woodcock C.L., and Skoultchi A.I.  (2005 Dec 29)  Histone H1 Depletion in Mammals Alters Global Chromatin Structure But Causes Specific Changes in Gene Regulation.  Cell 123(7): 1199-1212.  (Accompanied by Preview).<PDF>.<Supplementary><Cell_Preview>

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

Konishi A., Shimizu S., Hirota J., Takao T., Fan Y., Matsuoka Y., Zhang L., Yoneda Y., Fujii Y., Skoultchi A.I., and Tsujimoto Y. (2003 Sep 19)   Involvement of Histone H1.2 in Apoptosis Induced by DNA Double-strand Breaks.  Cell  114(6): 673-688.  (Featured Article)<PDF>.

Fan Y., Nikitina T., Morin-Kensicki EM, Zhao J., Woodcock CL, Magnuson TR, and Skoultchi AI (2003)  H1 Linker Histones Are Essential for Mouse Development and Affect Nucleosome Spacing In Vivo.  Mol. Cell. Biol. 23(13): 4559-72. <PDF>.

Alami R.*, Fan Y.*,  Pack S., Sonbuchner T., Besse A., Lin Q., Greally JM, Skoultchi AI, Bouhassira EE. (2003)  Linker Histones Subtypes Differentially Affect Gene Expression In Mammals.  Proc Natl Acad Sci U S A.  100(10): 5920-5.     (*Joint first authors).<PDF>

Gabrilovich DI, Cheng P., Fan Y., Yu B., Nikitina E., Sirotkin A., Shurin M., Oyama T., Adachi Y., Nadaf S., Carbone DP, and Skoultchi AI: (2002)   H1(0) Histone and Differentiation of Dendritic Cells. A Molecular Target for Tumor-derived Factors.  J Leukoc Biol. 72(2): 285-96. <PDF>.

Fan Y., Sirotkin A., Russell R., Ayala J. and Skoultchi, A., (2001). Individual somatic H1 subtypes are dispensable for mouse development even in mice lacking the H1(0) replacement subtype.  Mol. Cell. Biol. 21(23): 7933-43. <PDF>.

Fan Y., Braut S., Lin Q., Singer R.H., and Skoultchi A., (2001).  Determination of Transgenetic loci by Expression FISH.  Genomics  71, 66-69.<PDF>.