Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-myc transcription

被引:107
作者
Nair, M
Teng, A
Bilanchone, V
Agrawal, A
Li, BA
Dai, X [1 ]
机构
[1] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA
[3] Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA
关键词
D O I
10.1083/jcb.200508196
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transcriptional control plays a key role in regulating epidermal proliferation and differentiation. Although ample information has been obtained on how epidermal homeostasis is controlled in adult skin, less is known about the control of proliferation/differentiation of epidermal stem/progenitor cells in the developing embryo. Ovol1, encoding a zinc finger protein homologous to Drosophila melanogaster Ovo, is expressed in embryonic epidermal progenitor cells that are transiting from proliferation to terminal differentiation. In this study, we demonstrate a function for Ovol1 in interfollicular epidermal development. In its absence, developing epidermis fails to properly restrict the proliferative potential of progenitor cells, and cultured keratinocytes fail to efficiently undergo growth arrest in response to extrinsic growth-inhibitory signals. We present molecular evidence that c-myc expression is up-regulated in Ovol1-deficient suprabasal cells and that Ovol1 represses c-myc transcription by directly binding to its promoter. Collectively, our findings indicate that Ovol1 is required for proliferation exit of committed epidermal progenitor cells and identify c-myc as an Ovol1 target.
引用
收藏
页码:253 / 264
页数:12
相关论文
共 49 条
[1]   c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription [J].
Arabi, A ;
Wu, SQ ;
Ridderstråle, K ;
Bierhoff, H ;
Shiue, C ;
Fatyol, K ;
Fahlén, S ;
Hydbring, P ;
Söderberg, O ;
Grummt, I ;
Larsson, LG ;
Wright, APH .
NATURE CELL BIOLOGY, 2005, 7 (03) :303-310
[2]   NUCLEOLAR LOCALIZATION OF MYC TRANSCRIPTS [J].
BOND, VC ;
WOLD, B .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (06) :3221-3230
[3]  
BYRNE C, 1994, DEVELOPMENT, V120, P2369
[4]  
Caldelari R, 2000, J INVEST DERMATOL, V114, P1064, DOI 10.1046/j.1523-1747.2000.00960-4.x
[5]   The ovo gene required for cuticle formation and oogenesis in flies is involved in hair formation and spermatogenesis in mice [J].
Dai, X ;
Schonbaum, C ;
Degenstein, L ;
Bai, WY ;
Mahowald, A ;
Fuchs, E .
GENES & DEVELOPMENT, 1998, 12 (21) :3452-3463
[6]   Transcriptional control of epidermal specification and differentiation [J].
Dai, X ;
Segre, JA .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2004, 14 (05) :485-491
[7]   THE PROXIMAL PROMOTER OF THE MOUSE LORICRIN GENE CONTAINS A FUNCTIONAL AP-1 ELEMENT AND DIRECTS KERATINOCYTE-SPECIFIC BUT NOT DIFFERENTIATION-SPECIFIC EXPRESSION [J].
DISEPIO, D ;
JONES, A ;
LONGLEY, MA ;
BUNDMAN, D ;
ROTHNAGEL, JA ;
ROOP, DR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (18) :10792-10799
[8]  
EUSTICE DC, 1991, BIOTECHNIQUES, V11, P739
[9]   Defining the temporal requirements for Myc in the progression and maintenance of skin neoplasia [J].
Flores, I ;
Murphy, DJ ;
Swigart, LB ;
Knies, U ;
Evan, GI .
ONCOGENE, 2004, 23 (35) :5923-5930
[10]   Getting under the skin of epidermal morphogenesis [J].
Fuchs, E ;
Raghavan, S .
NATURE REVIEWS GENETICS, 2002, 3 (03) :199-209