Regulation of Gene Expression during the Cell Cycle and during the Proliferation/Differentiation Transition
Ph.D., 1975, Princeton University
Our laboratory is investigating the control of cell proliferation and its relationship to the onset and progression of differentiation. Our experimental approach is to examine molecular mechanisms involved in regulating specific genes that are expressed in actively proliferating cells, changes in the expression of these genes during the down-regulation of cell growth, and the initiation of expression of cell and tissue specific genes as cells differentiate.
One area of emphasis is the regulation of human histone gene expression. Histones are expressed primarily during the S phase of the cell cycle and are intimately involved with genome replication. We have focused on transcriptional regulation of the H4, H3 and H1 histone genes. In the H4 and H3 genes two sites of in vivo protein-DNA interaction have been identified in the proximal promoter region. Site I sequences influence the level of transcription while Site II sequences contain the cell cycle regulatory element and are also important for on/off regulation of this gene. We are continuing our characterization of the complex array of transcription factors and cell cycle regulatory proteins that bind these regulatory sequences to modulate expression both during the cell cycle and in the transition between proliferation and differentiation.
A second area of interest is the osteocalcin gene, which is normally expressed only in post-proliferative cells, primarily those of bone. We are investigating the many-faceted regulation of this gene both in terms of tissue-specificity and with regard to its activation as cells cease proliferating and assume a mature bone cell phenotype. The changes in chromatin structure and nuclear matrix association of the histone and osteocalcin genes that accompany changes in gene expression are being defined.
Transcription factor retention on mitotic chromosomes. A unique dimension to epigenetic control. An osteoblast cell undergoing mitosis was stained with antibodies specific for the osteoblast master regulatory protein Runx2 (green) and the cytoskeletal structural protein Tubilin (red). Cells were counterstained with DAPI to visualize DNA.
Tai PW, Zaidi SK, Wu H, Grandy RA, Montecino MM, van Wijnen AJ, Lian JB, Stein GS, Stein JL (2013) The Dynamic Architectural and Epigenetic Nuclear Landscape: Developing the Genomic Almanac of Biology and Disease. J Cell Physiol in press.
Dowdy CR, Frederick D, Zaidi SK, Colby JL, Lian JB, van Wijnen AJ, Gerstein RM, Stein JL, Stein GS (2013) A germline point mutation in Runx1 uncouples its role in definitive hematopoiesis from differentiation. Exp Hematol 41(11): 980-991.e1.
van der Deen M, Taipaleenmäki H, Zhang Y, Teplyuk NM, Gupta A, Cinghu S, Shogren K, Maran A, Yaszemski MJ, Ling L, Cool SM, Leong DT, Dierkes C, Zustin J, Salto-Tellez M, Ito Y, Bae SC, Zielenska M, Squire JA, Lian JB, Stein JL, Zambetti GP, Jones SN, Galindo M, Hesse E, Stein GS, van Wijnen AJ (2013) MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J Biol Chem 288(29): 21307-19.
Yoon WJ, Islam R, Cho YD, Woo KM, Baek JH, Uchida T, Komori T, van Wijnen A, Stein JL, Lian JB, Stein GS, Choi JY, Bae SC, Ryoo HM (2013) Pin1-mediated Runx2 modification is critical for skeletal development. J Cell Physiol 228(12): 2377-85.
Li M, Luo XJ, Rietschel M, Lewis CM, Mattheisen M, Müller-Myhsok B, Jamain S, Leboyer M, Landén M, Thompson PM, Cichon S, Nöthen MM, Schulze TG, Sullivan PF, Bergen SE, Donohoe G, Morris DW, Hargreaves A, Gill M, Corvin A, Hultman C, Toga AW, Shi L, Lin Q, Shi H, Gan L, Meyer-Lindenberg A, Czamara D, Henry C, Etain B, Bis JC, Ikram MA, Fornage M, Debette S, Launer LJ, Seshadri S, Erk S, Walter H, Heinz A, Bellivier F, Stein JL, Medland SE, Vasquez AA, Hibar DP, Franke B, Martin NG, Wright MJ (2013) Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. Mol Psychiatry in press.
Zaidi SK, Van Wijnen AJ, Lian JB, Stein JL, Stein GS (2013) Targeting deregulated epigenetic control in cancer. J Cell Physiol 228(11): 2103-8.
Li M, Luo XJ, Rietschel M, Lewis CM, Mattheisen M, Müller-Myhsok B, Jamain S, Leboyer M, Landén M, Thompson PM, Cichon S, Nöthen MM, Schulze TG, Sullivan PF, Bergen SE, Donohoe G, Morris DW, Hargreaves A, Gill M, Corvin A, Hultman C, Toga AW, Shi L, Lin Q, Shi H, Gan L, Meyer-Lindenberg A, Czamara D, Henry C, Etain B, Bis JC, Ikram MA, Fornage M, Debette S, Launer LJ, Seshadri S, Erk S, Walter H, Heinz A, Bellivier F, Stein JL, Medland SE, Arias Vasquez A, Hibar DP, Franke B, Martin NG, Wright MJ, MooDS Bipolar Consortium, Strohmaier J, Breuer R, Meier S, Mühleisen TW, Degenhardt FA, Hoffmann P, Herms S, Schwarz M, Vedder H, Kammerer-Ciernioch J, Reif A, Sasse J, Bauer M, Zwick S, Hautzinger M, Wright A, Mitchell PB, Fullerton JM, Schofield PR, Montgomery GW, Martin NG, Czerski PM, Hauser J, Schumacher J, Maier W, Propping P, The Swedish Bipolar Study Group, Backlund L, Frisén L, Lavebratt C, Schalling M, Osby U, The Alzheimer’s Disease Neuroimaging Initiative, ENIGMA Consortium, CHARGE Consortium, Su B (2013) Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility. Mol Psychiatry in press.
Department of Biochemistry
Office: Given E210E
Lab: Given E209
Phillip Tai, Postdoctoral Fellow
- 12/10/2013 11:30 AM - 12:30 PM
Dr. Kelly Fimlaid
- 12/17/2013 11:30 AM - 12:30 PM
- 1/28/2014 11:30 AM - 12:30 PM
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