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

Gordon JA, Stein JL, Westendorf JJ, van Wijnen AJ (2015) Chromatin modifiers and histone modifications in bone formation, regeneration, and therapeutic intervention for bone-related disease. Bone in press.

Wu Q, Madany P, Akech J, Dobson JR, Douthwright S, Browne G, Colby JL, Winter GE, Bradner JE, Pratap J, Sluder G, Bhargava R, Chiosea S, van Wijnen AJ, Stein JL, Stein GS, Lian JB, Nickerson JA, Imbalzano AN (2015) The SWI/SNF ATPases are Required for Triple Negative Breast Cancer Cell Proliferation. J Cell Physiol in press.

Scott RE, Ghule PN, Stein JL, Stein GS (2015) Cell cycle gene expression networks discovered using systems biology: Significance in carcinogenesis. J Cell Physiol in press.

Zhang X, Wu H, Dobson JR, Browne G, Hong D, Akech J, Languino LR, Stein JL, Stein GS, Lian JB (2015) Expression of the IL-11 Gene in Metastatic Cells Is Supported by Runx2-Smad and Runx2-cJun Complexes Induced by TGFβ1. J Cell Biochem in press.

Browne G, Taipaleenmäki H, Bishop NM, Madasu SC, Shaw LM, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2015) Runx1 is associated with breast cancer progression in MMTV-PyMT transgenic mice and its depletion in vitro inhibits migration and invasion. J Cell Physiol in press.

Martinez RA, Stein JL, Krostag AR, Nelson AM, Marken JS, Menon V, May RC, Yao Z, Kaykas A, Geschwind DH, Grimley JS (2015) Genome engineering of isogenic human ES cells to model autism disorders. Nucleic Acids Res in press.

Smith I, Silveirinha V, Stein JL, de la Torre-Ubieta L, Farrimond JA, Williamson EM, Whalley BJ (2015) Human neural stem cell-derived cultures in three-dimensional substrates form spontaneously functional neuronal networks. J Tissue Eng Regen Med in press.

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

  • 4/28/2015 11:30 AM – 12:30 PM
    Davis Auditorium
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  • 5/5/2015 11:30 AM – 12:30 PM
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    Victoria DeVault
  • 5/12/2015 11:30 AM – 12:30 PM
    Davis Auditorium
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    Arvis Sulovari

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