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



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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

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 36S1: S151-S158.

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.

Dobson JR, Taipaleenmäki H, Hu YJ, Hong D, van Wijnen AJ, Stein JL, Stein GS, Lian JB, Pratap J (2014) hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3. Cancer Cell Int 14: 73.

Barutcu AR, Tai PW, Wu H, Gordon JA, Whitfield TW, Dobson JR, Imbalzano AN, Lian JB, van Wijnen AJ, Stein JL, Stein GS (2014) The bone-specific Runx2-P1 promoter displays conserved three-dimensional chromatin structure with the syntenic Supt3h promoter. Nucleic Acids Res 42(16): 10360-72.

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

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Lab Members

   Phillip Tai, Postdoctoral Fellow

Upcoming Events

  • 1/13/2015 11:30 AM – 12:30 PM
    Davis Auditorium
    TBA
    Drew Barber
  • 1/20/2015 11:30 AM – 12:30 PM
    Davis Auditorium
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    Sharath Madasu
  • 1/27/2015 11:30 AM – 12:30 PM
    Davis Auditorium
    TBA
    Filiz Korkmaz

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