Yuhong Fan, Associate Professor and Georgia Cancer Coalition Distinguished Cancer Scholar
Ph.D., Cell Biology, Albert Einstein College of Medicine
Office: Parker H. Petit Biotechnology (IBB) 2313
Epigenetics, Chromatin, Gene Expression, Function of Linker Histones in Mammalian Development and Stem Cell Differentiation
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.
Cao K, Lailler N, Zhang Y, Kumar A, Uppal K, Liu Z, Lee EK, Wu H, Medrzycki M, Pan C, Ho PY, Cooper GP Jr, Dong X, Bock C, Bouhassira EE, Fan Y. (2013) High-resolution mapping of h1 linker histone variants in embryonic stem cells. PLoS Genetics 9(4):e1003417. doi: 10.1371/journal.pgen.1003417. PMID: 23633960
Majumder A, Dhara SK, Swetenburg R, Mithani M, Cao K, Medrzycki M, Fan Y, Stice SL. (2013) Inhibition of DNA methyltransferases and histone deacetylases induces astrocytic differentiation of neural progenitors. Stem Cell Res. 11(1):574-586. doi: 10.1016/j.scr.2013.03.003. PMID: 23644509
Zhang Y., Liu Z., Medrzyski M., Cao K., Fan Y. (2012) Reduction of Hox gene expression by H1 depletion PLoS One 7(6):e38829.
Zhang Y., Cooke M., Panjwani S., Cao K., Krauth B., Pan C., Ho PY., Berhe DT., Medrzyski M., McDevitt TC., Fan Y.(2012) Histone H1 depletion impairs embryonic stem cell differentiation. PLoS Genetics 8 (5):e1002691.
Medrzyski M., Zhang Y., Cao K., Fan Y. (2012) Expression Analysis of Mammalian Linker-histone Subtypes. J Vis Exp. (61), pii: 3577. DOI :10.3791/3577.
MacLean JA., Bettegowda A., Kim BJ., Lou CH., Yang SM., Bhardwaj A., Shanker S., Hu Z., Fan Y., Eckardt S., McLaughlin KJ., Skoultchi AI., and Wilkinson MF. (2011) The rhox homeobox gene cluster is Imprinted and Selectively Targeted for Regulation by Histone H1 and DNA Methylation. Mol. Cell. Biol. 31(6):1275-87
Medrzyski M., Zhang Y., McDonald JF., Fan Y. (2012) Profiling of linker histones variants in ovarian cancer. Front. Biosci. 17:396-406.
Eskeland R., Leeb M., Grimes GR., Kress C., Boyle S., Sproul D., Gilbert N., Fan Y., Skoultchi AI., Wutz A., Bickmore WA (2010) Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol. Cell 38(3):452-64.
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.
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.