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MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions.

Ishibashi J, Perry RL, Asakura A, Rudnicki MA - J. Cell Biol. (2005)

Bottom Line: MyoD, however, is strikingly more effective than Myf5 at inducing differentiation-phase target genes.This distinction between MyoD and Myf5 results from a novel and unanticipated cooperation between the MyoD NH2- and COOH-terminal regions.Together, these results support the notion that Myf5 functions toward myoblast proliferation, whereas MyoD prepares myoblasts for efficient differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.

ABSTRACT
MyoD and Myf5 are basic helix-loop-helix transcription factors that play key but redundant roles in specifying myogenic progenitors during embryogenesis. However, there are functional differences between the two transcription factors that impact myoblast proliferation and differentiation. Target gene activation could be one such difference. We have used microarray and polymerase chain reaction approaches to measure the induction of muscle gene expression by MyoD and Myf5 in an in vitro model. In proliferating cells, MyoD and Myf5 function very similarly to activate the expression of likely growth phase target genes such as L-myc, m-cadherin, Mcpt8, Runx1, Spp1, Six1, IGFBP5, and Chrnbeta1. MyoD, however, is strikingly more effective than Myf5 at inducing differentiation-phase target genes. This distinction between MyoD and Myf5 results from a novel and unanticipated cooperation between the MyoD NH2- and COOH-terminal regions. Together, these results support the notion that Myf5 functions toward myoblast proliferation, whereas MyoD prepares myoblasts for efficient differentiation.

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Decreased expression of differentiation markers by MyoD−/− primary myoblasts. Expression levels in MyoD- primary myoblasts of the genes in Table I show that the majority of differentiation markers are greatly reduced relative to wild-type myoblasts (e.g., Myh3 to myogenin). In contrast, genes that are regulated in growth phase by MyoD and Myf5 are reduced to a lesser degree, if at all (e.g., Mcpt8, Six1, and Runx1). Calls are shown for wild-type (n = 3) or MyoD−/− (n = 3) myoblasts. P, present; M, marginal; A, absent. Change calls are shown for nine pairwise comparisons between wild-type and MyoD−/− myoblasts. I, increase; MI, marginal increase; NC, no change; MD, marginal decrease; D, decrease.
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fig2: Decreased expression of differentiation markers by MyoD−/− primary myoblasts. Expression levels in MyoD- primary myoblasts of the genes in Table I show that the majority of differentiation markers are greatly reduced relative to wild-type myoblasts (e.g., Myh3 to myogenin). In contrast, genes that are regulated in growth phase by MyoD and Myf5 are reduced to a lesser degree, if at all (e.g., Mcpt8, Six1, and Runx1). Calls are shown for wild-type (n = 3) or MyoD−/− (n = 3) myoblasts. P, present; M, marginal; A, absent. Change calls are shown for nine pairwise comparisons between wild-type and MyoD−/− myoblasts. I, increase; MI, marginal increase; NC, no change; MD, marginal decrease; D, decrease.

Mentions: All of the genes identified in Table I are robustly expressed by proliferating wild-type primary myoblasts (Fig. 2). Most (47/53 = 89%) of these genes are decreased in MyoD−/− myoblasts, whereas the remainder (6/53) exhibit a mixture of increase/no change/decrease calls and moderate fold increases. Differentiation markers are vastly decreased (up to 140-fold for myosin heavy chain-3 or troponin T1), whereas most putative growth-phase genes showed only moderate changes (e.g., approximately eightfold for m-cadherin or L-myc and ∼2.7–1.8-fold for Six1 or Runx1).


MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions.

Ishibashi J, Perry RL, Asakura A, Rudnicki MA - J. Cell Biol. (2005)

Decreased expression of differentiation markers by MyoD−/− primary myoblasts. Expression levels in MyoD- primary myoblasts of the genes in Table I show that the majority of differentiation markers are greatly reduced relative to wild-type myoblasts (e.g., Myh3 to myogenin). In contrast, genes that are regulated in growth phase by MyoD and Myf5 are reduced to a lesser degree, if at all (e.g., Mcpt8, Six1, and Runx1). Calls are shown for wild-type (n = 3) or MyoD−/− (n = 3) myoblasts. P, present; M, marginal; A, absent. Change calls are shown for nine pairwise comparisons between wild-type and MyoD−/− myoblasts. I, increase; MI, marginal increase; NC, no change; MD, marginal decrease; D, decrease.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171269&req=5

fig2: Decreased expression of differentiation markers by MyoD−/− primary myoblasts. Expression levels in MyoD- primary myoblasts of the genes in Table I show that the majority of differentiation markers are greatly reduced relative to wild-type myoblasts (e.g., Myh3 to myogenin). In contrast, genes that are regulated in growth phase by MyoD and Myf5 are reduced to a lesser degree, if at all (e.g., Mcpt8, Six1, and Runx1). Calls are shown for wild-type (n = 3) or MyoD−/− (n = 3) myoblasts. P, present; M, marginal; A, absent. Change calls are shown for nine pairwise comparisons between wild-type and MyoD−/− myoblasts. I, increase; MI, marginal increase; NC, no change; MD, marginal decrease; D, decrease.
Mentions: All of the genes identified in Table I are robustly expressed by proliferating wild-type primary myoblasts (Fig. 2). Most (47/53 = 89%) of these genes are decreased in MyoD−/− myoblasts, whereas the remainder (6/53) exhibit a mixture of increase/no change/decrease calls and moderate fold increases. Differentiation markers are vastly decreased (up to 140-fold for myosin heavy chain-3 or troponin T1), whereas most putative growth-phase genes showed only moderate changes (e.g., approximately eightfold for m-cadherin or L-myc and ∼2.7–1.8-fold for Six1 or Runx1).

Bottom Line: MyoD, however, is strikingly more effective than Myf5 at inducing differentiation-phase target genes.This distinction between MyoD and Myf5 results from a novel and unanticipated cooperation between the MyoD NH2- and COOH-terminal regions.Together, these results support the notion that Myf5 functions toward myoblast proliferation, whereas MyoD prepares myoblasts for efficient differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.

ABSTRACT
MyoD and Myf5 are basic helix-loop-helix transcription factors that play key but redundant roles in specifying myogenic progenitors during embryogenesis. However, there are functional differences between the two transcription factors that impact myoblast proliferation and differentiation. Target gene activation could be one such difference. We have used microarray and polymerase chain reaction approaches to measure the induction of muscle gene expression by MyoD and Myf5 in an in vitro model. In proliferating cells, MyoD and Myf5 function very similarly to activate the expression of likely growth phase target genes such as L-myc, m-cadherin, Mcpt8, Runx1, Spp1, Six1, IGFBP5, and Chrnbeta1. MyoD, however, is strikingly more effective than Myf5 at inducing differentiation-phase target genes. This distinction between MyoD and Myf5 results from a novel and unanticipated cooperation between the MyoD NH2- and COOH-terminal regions. Together, these results support the notion that Myf5 functions toward myoblast proliferation, whereas MyoD prepares myoblasts for efficient differentiation.

Show MeSH