Expression profiling and identification of novel genes involved in myogenic differentiation

被引:48
作者
Tomczak, KK
Marinescu, VD
Ramoni, MF
Sanoudou, D
Montanaro, F
Han, M
Kunkel, LM
Kohane, IS
Beggs, AH
机构
[1] Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA
[2] Childrens Hosp Boston, Genom Program, Boston, MA 02115 USA
[3] Childrens Hosp, Informat Program, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA USA
关键词
C2C12; myoblasts; myogenesis; microarrays; cluster analysis; Expressed Sequence Tags;
D O I
10.1096/f.03-0568fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Skeletal muscle differentiation is a complex, highly coordinated process that relies on precise temporal gene expression patterns. To better understand this cascade of transcriptional events, we used expression profiling to analyze gene expression in a 12-day time course of differentiating C2C12 myoblasts. Cluster analysis specific for time-ordered microarray experiments classified 2895 genes and ESTs with variable expression levels between proliferating and differentiating cells into 22 clusters with distinct expression patterns during myogenesis. Expression patterns for several known and novel genes were independently confirmed by real-time quantitative RT-PCR and/or Western blotting and immunofluorescence. MyoD and MEF family members exhibited unique expression kinetics that were highly coordinated with cell-cycle withdrawal regulators. Among genes with peak expression levels during cell cycle withdrawal were Vcam1, Itgb3, Itga5, Vcl, as well as Ptger4, a gene not previously associated with the process of myogenesis. One interesting uncharacterized transcript that is highly induced during myogenesis encodes several immunoglobulin repeats with sequence similarity to titin, a large sarcomeric protein. These data sets identify many additional uncharacterized transcripts that may play important functions in muscle cell proliferation and differentiation and provide a baseline for comparison with C2C12 cells expressing various mutant genes involved in myopathic disorders.
引用
收藏
页码:403 / +
页数:23
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共 50 条
[1]   The expression and regulation of follistatin and a follistatin-like gene during avian somite compartmentalization and myogenesis [J].
Amthor, H ;
Connolly, D ;
Patel, K ;
BrandSaberi, B ;
Wilkinson, DG ;
Cooke, J ;
Christ, B .
DEVELOPMENTAL BIOLOGY, 1996, 178 (02) :343-362
[2]   Studies of the dynamics of skeletal muscle regeneration: the mouse came back! [J].
Anderson, JE .
BIOCHEMISTRY AND CELL BIOLOGY, 1998, 76 (01) :13-26
[3]   Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis [J].
Andres, V ;
Walsh, K .
JOURNAL OF CELL BIOLOGY, 1996, 132 (04) :657-666
[4]   CYTOPLASMIC ACTIVATION OF HUMAN NUCLEAR GENES IN STABLE HETEROCARYONS [J].
BLAU, HM ;
CHIU, CP ;
WEBSTER, C .
CELL, 1983, 32 (04) :1171-1180
[5]  
BOBER E, 1991, J CELL BIOL, V6, P1255
[6]  
Chambers R L, 1996, Can J Appl Physiol, V21, P155
[7]   Dynamic gene expression during the onset of myoblast differentiation in vitro [J].
Delgado, I ;
Huang, XX ;
Jones, S ;
Zhang, LN ;
Hatcher, R ;
Gao, BF ;
Zhang, PM .
GENOMICS, 2003, 82 (02) :109-121
[8]   MYOBLAST FUSION IS REGULATED BY A PROSTANOID OF THE ONE SERIES INDEPENDENTLY OF A RISE IN CYCLIC-AMP [J].
ENTWISTLE, A ;
CURTIS, DH ;
ZALIN, RJ .
JOURNAL OF CELL BIOLOGY, 1986, 103 (03) :857-866
[9]   Induction of p18(INK4c) and its predominant association with CDK4 and CDK6 during myogenic differentiation [J].
Franklin, DS ;
Xiong, Y .
MOLECULAR BIOLOGY OF THE CELL, 1996, 7 (10) :1587-1599
[10]   Calcineurin initiates skeletal muscle differentiation by activating MEF2 and MyoD [J].
Friday, BB ;
Mitchell, PO ;
Kegley, KM ;
Pavlath, GK .
DIFFERENTIATION, 2003, 71 (03) :217-227