Regulation of Gene Expression during the Cell Cycle and during the Proliferation/Differentiation Transition



Profile

Ph.D., 1975, Princeton University

Research Description

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.

<b>Transcription factor retention on mitotic chromosomes</b>.  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.” ></center></p>
<p><font size=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.

Recent Publications

Yang S, Quaresma AJ, Nickerson JA, Green KM, Shaffer SA, Imbalzano AN, Martin-Buley LA, Lian JB, Stein JL, van Wijnen AJ, Stein GS (2015) Subnuclear domain proteins in cancer cells support transcription factor RUNX2 functions in DNA damage response. J Cell Sci in press.

Hibar DP, Stein JL, Renteria ME, Arias-Vasquez A, Desrivières S, Jahanshad N, Toro R, Wittfeld K, Abramovic L, Andersson M, Aribisala BS, Armstrong NJ, Bernard M, Bohlken MM, Boks MP, Bralten J, Brown AA, Mallar Chakravarty M, Chen Q, Ching CR, Cuellar-Partida G, den Braber A, Giddaluru S, Goldman AL, Grimm O, Guadalupe T, Hass J, Woldehawariat G, Holmes AJ, Hoogman M, Janowitz D, Jia T, Kim S, Klein M, Kraemer B, Lee PH, Olde Loohuis LM, Luciano M, Macare C, Mather KA, Mattheisen M, Milaneschi Y, Nho K, Papmeyer M, Ramasamy A, Risacher SL, Roiz-Santiañez R, Rose EJ, Salami A, Sämann PG, Schmaal L, Schork AJ, Shin J, Strike LT, Teumer A, van Donkelaar MM, van Eijk KR, Walters RK, Westlye LT, Whelan CD, Winkler AM, Zwiers MP, Alhusaini S, Athanasiu L, Ehrlich S, Hakobjan MM, Hartberg CB, Haukvik UK, Heister AJ, Hoehn D, Kasperaviciute D, Liewald DC, Lopez LM, Makkinje RR, Matarin M, Naber MA, Reese McKay D, Needham M, Nugent AC, Pütz B, Royle NA, Shen L, Sprooten E, Trabzuni D, van der Marel SS, van Hulzen KJ, Walton E, Wolf C, Almasy L, Ames D, Arepalli S, Assareh AA, Bastin ME, Brodaty H, Bulayeva KB, Carless MA, Cichon S, Corvin A, Curran JE, Czisch M, de Zubicaray GI, Dillman A, Duggirala R, Dyer TD, Erk S, Fedko IO, Ferrucci L, Foroud TM, Fox PT, Fukunaga M, Raphael Gibbs J, Göring HH, Green RC, Guelfi S, Hansell NK, Hartman CA, Hegenscheid K, Heinz A, Hernandez DG, Heslenfeld DJ, Hoekstra PJ, Holsboer F, Homuth G, Hottenga JJ, Ikeda M, Jack CR Jr, Jenkinson M, Johnson R, Kanai R, Keil M, Kent JW Jr, Kochunov P, Kwok JB, Lawrie SM, Liu X, Longo DL, McMahon KL, Meisenzahl E, Melle I, Mohnke S, Montgomery GW, Mostert JC, Mühleisen TW, Nalls MA, Nichols TE, Nilsson LG, Nöthen MM, Ohi K, Olvera RL, Perez-Iglesias R, Bruce Pike G, Potkin SG, Reinvang I, Reppermund S, Rietschel M, Romanczuk-Seiferth N, Rosen GD, Rujescu D, Schnell K, Schofield PR, Smith C, Steen VM, Sussmann JE, Thalamuthu A, Toga AW, Traynor BJ, Troncoso J, Turner JA, Valdés Hernández MC, van ‘t Ent D, van der Brug M, van der Wee NJ, van Tol MJ, Veltman DJ, Wassink TH, Westman E, Zielke RH, Zonderman AB, Ashbrook DG, Hager R, Lu L, McMahon FJ, Morris DW, Williams RW, Brunner HG, Buckner RL, Buitelaar JK, Cahn W, Calhoun VD, Cavalleri GL, Crespo-Facorro B, Dale AM, Davies GE, Delanty N, Depondt C, Djurovic S, Drevets WC, Espeseth T, Gollub RL, Ho BC, Hoffmann W, Hosten N, Kahn RS, Le Hellard S, Meyer-Lindenberg A, Müller-Myhsok B, Nauck M, Nyberg L, Pandolfo M, Penninx BW, Roffman JL, Sisodiya SM, Smoller JW, van Bokhoven H, van Haren NE, Völzke H, Walter H, Weiner MW, Wen W, White T, Agartz I, Andreassen OA, Blangero J, Boomsma DI, Brouwer RM, Cannon DM, Cookson MR, de Geus EJ, Deary IJ, Donohoe G, Fernández G, Fisher SE, Francks C, Glahn DC, Grabe HJ, Gruber O, Hardy J, Hashimoto R, Hulshoff Pol HE, Jönsson EG, Kloszewska I, Lovestone S, Mattay VS, Mecocci P, McDonald C, McIntosh AM, Ophoff RA, Paus T, Pausova Z, Ryten M, Sachdev PS, Saykin AJ, Simmons A, Singleton A, Soininen H, Wardlaw JM, Weale ME, Weinberger DR, Adams HH, Launer LJ, Seiler S, Schmidt R, Chauhan G, Satizabal CL, Becker JT, Yanek L, van der Lee SJ, Ebling M, Fischl B, Longstreth WT Jr, Greve D, Schmidt H, Nyquist P, Vinke LN, van Duijn CM, Xue L, Mazoyer B, Bis JC, Gudnason V, Seshadri S, Arfan Ikram M, The Alzheimer’s Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Martin NG, Wright MJ, Schumann G, Franke B, Thompson PM, Medland SE (2015) Common genetic variants influence human subcortical brain structures. Nature in press.

Lim KE, Park NR, Che X, Han MS, Jeong JH, Kim SY, Park CY, Akiyama H, Kim JE, Ryoo HM, Stein JL, Lian JB, Stein GS, Choi JY (2014) Core Binding Factor β of Osteoblasts Maintains Cortical Bone Mass Via Stabilization of Runx2 in Mice. J Bone Miner Res in press.

Ashbrook DG, Williams RW, Lu L, Stein JL, Hibar DP, Nichols TE, Medland SE, Thompson PM, Hager R (2014) Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease. BMC Genomics 15: 850.

Hibar DP, Stein JL, Jahanshad N, Kohannim O, Hua X, Toga AW, McMahon KL, de Zubicaray GI, Martin NG, Wright MJ, Alzheimer’s Disease Neuroimaging Initiative, Weiner MW, Thompson PM (2015) Genome-wide interaction analysis reveals replicated epistatic effects on brain structure. Neurobiol Aging 36 Suppl 1: S151-8.

Gordon JA, Montecino MA, Aqeilan RI, Stein JL, Stein GS, Lian JB (2014) Epigenetic pathways regulating bone homeostasis: potential targeting for intervention of skeletal disorders. Curr Osteoporos Rep 12(4): 496-506.

Tye CE, Gordon JA, Martin-Buley LA, Stein JL, Lian JB, Stein GS (2015) Could lncRNAs be the missing links in control of mesenchymal stem cell differentiation? J Cell Physiol 230(3): 526-34.

View all Stein publications here.


Janet Stein, Ph.D.

Janet
Stein, Ph.D.

Professor
Department of Biochemistry

 

802-656-4876
Office: Given E210E
Lab: Given E209

Lab Homepage

Lab Members

   Phillip Tai, Postdoctoral Fellow

Upcoming Events

  • 1/27/2015 11:30 AM – 12:30 PM
    Davis Auditorium
    TBA
    Filiz Korkmaz
  • 2/3/2015 11:30 AM – 12:30 PM
    Davis Auditorium
    TBA
    Bob Bauer
  • 2/10/2015 11:30 AM – 12:30 PM
    Davis Auditorium
    TBA
    Michael Secinaro

Recent CMB Blog Posts