Long Range Interactions Regulate Igf2 Gene Transcription during Skeletal Muscle Differentiation

被引:36
作者
Alzhanov, Damir T. [1 ]
McInerney, Stephanie F. [1 ]
Rotwein, Peter [1 ]
机构
[1] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA
基金
美国国家卫生研究院;
关键词
GROWTH-FACTOR-II; SIGNALING PATHWAYS; MYOD BINDING; LIFE-SPAN; H19; GENE; INSULIN; EXPRESSION; METHYLATION; HYPERTROPHY; ACTIVATION;
D O I
10.1074/jbc.M110.160986
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
The differentiation, maintenance, and repair of skeletal muscle is controlled by interactions between genetically determined transcriptional programs regulated by myogenic transcription factors and environmental cues activated by growth factors and hormones. Signaling through the insulin-like growth factor 1 (IGF1) receptor by locally produced IGF2 defines one such pathway that is critical for normal muscle growth and for regeneration after injury. IGF2 gene and protein expression are induced as early events in muscle differentiation, but the responsible molecular mechanisms are unknown. Here we characterize a distal DNA element within the imprinted mouse Igf2-H19 locus with properties of a muscle transcriptional enhancer. We find that this region undergoes a transition to open chromatin during differentiation, whereas adjacent chromatin remains closed, and that it interacts in differentiating muscle nuclei but not in mesenchymal precursor cells with the Igf2 gene found more than 100 kb away, suggesting that chromatin looping or sliding to bring the enhancer in proximity to Igf2 promoters is also an early event in muscle differentiation. Because this element directly stimulates the transcriptional activity of an Igf2 promoter-reporter gene in differentiating myoblasts, our results indicate that we have identified a bona fide distal transcriptional enhancer that supports Igf2 gene activation in skeletal muscle cells. Because this DNA element is conserved in the human IGF2-H19 locus, our results further suggest that its muscle enhancer function also is conserved among different mammalian species.
引用
收藏
页码:38969 / 38977
页数:9
相关论文
共 54 条
[41]   EVOLUTION OF INSULIN-LIKE GROWTH FACTOR-II - CHARACTERIZATION OF THE MOUSE IGF-II GENE AND IDENTIFICATION OF 2 PSEUDO-EXONS [J].
ROTWEIN, P ;
HALL, LJ .
DNA AND CELL BIOLOGY, 1990, 9 (10) :725-735
[42]   Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation [J].
Serra, Carlo ;
Palacios, Daniela ;
Mozzetta, Chiara ;
Forcales, Sonia V. ;
Morantte, Lanessa ;
Ripani, Meri ;
Jones, David R. ;
Du, Keyong ;
Jhala, Ulupi S. ;
Simone, Cristiano ;
Puri, Pier Lorenzo .
MOLECULAR CELL, 2007, 28 (02) :200-213
[43]   p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci [J].
Simone, C ;
Forcales, SV ;
Hill, DA ;
Imbalzano, AN ;
Latella, L ;
Puri, PL .
NATURE GENETICS, 2004, 36 (07) :738-743
[44]  
Stewart CEH, 1996, J CELL PHYSIOL, V169, P23, DOI 10.1002/(SICI)1097-4652(199610)169:1<23::AID-JCP3>3.3.CO
[45]  
2-W
[46]   The circuitry of a master switch: Myod and the regulation of skeletal muscle gene transcription [J].
Tapscott, SJ .
DEVELOPMENT, 2005, 132 (12) :2685-2695
[47]   A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig [J].
Van Laere, AS ;
Nguyen, M ;
Braunschweig, M ;
Nezer, C ;
Collette, C ;
Moreau, L ;
Archibald, AL ;
Haley, CS ;
Buys, N ;
Tally, M ;
Andersson, G ;
Georges, M ;
Andersson, L .
NATURE, 2003, 425 (6960) :832-836
[48]   We gather together: insulators and genome organization [J].
Wallace, Julie A. ;
Felsenfeld, Gary .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2007, 17 (05) :400-407
[49]   Location of enhancers is essential for the imprinting of H19 and Igf2 genes [J].
Webber, AL ;
Ingram, RS ;
Levorse, JM ;
Tilghman, SM .
NATURE, 1998, 391 (6668) :711-715
[50]   Selective control of skeletal muscle differentiation by Akt1 [J].
Wilson, Elizabeth M. ;
Rotwein, Peter .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (08) :5106-5110