Differential cooperation between heterochromatin protein HP1 isoforms and MyoD in myoblasts.
Mechanisms of transcriptional repression are important during cell differentiation. Mammalian heterochromatin protein 1 isoforms HP1alpha, HP1beta, and HP1gamma play important roles in the regulation of chromatin structure and function. We explored the possibility of different roles for the three HP1 isoforms in an integrated system, skeletal muscle terminal differentiation. In this system, terminal differentiation is initiated by the transcription factor MyoD, whose target genes remain mainly silent until myoblasts are induced to differentiate. Here we show that HP1alpha and HP1beta isoforms, but not HP1gamma, interact with MyoD in myoblasts. This interaction is direct, as shown using recombinant proteins in vitro. A gene reporter assay revealed that HP1alpha and HP1beta, but not HP1gamma, inhibit MyoD transcriptional activity, suggesting a model in which MyoD could serve as a bridge between nucleosomes and chromatin-binding proteins such as HDACs and HP1. Chromatin immunoprecipitation assays show a preferential recruitment of HP1 proteins on MyoD target genes in proliferating myoblasts. Finally, modulation of HP1 protein level impairs MyoD target gene expression and muscle terminal differentiation. Together, our data show a nonconventional interaction between HP1 and a tissue-specific transcription factor, MyoD. In addition, they strongly suggest that HP1 isoforms play important roles during muscle terminal differentiation in an isoform-dependent manner.
Yahi
Hakima
H
Institut André Lwoff, CNRS, FRE 2944, 7 rue Guy Moquet, Villejuif, France.
Fritsch
Lauriane
L
Philipot
Ophelie
O
Guasconi
Valentina
V
Souidi
Mouloud
M
Robin
Philippe
P
Polesskaya
Anna
A
Losson
Regine
R
Harel-Bellan
Annick
A
Ait-Si-Ali
Slimane
S
D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D017570:MyoD Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
C000715593:CBX1 protein, human; C000715594:CBX5 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D020033:Protein Isoforms; D011994:Recombinant Proteins; D000090266:Chromobox Protein Homolog 5