Emerin and histone deacetylase 3 (HDAC3) cooperatively regulate expression and nuclear positions of MyoD, Myf5, and Pax7 genes during myogenesis.
The spatial organization of chromatin is critical in establishing cell-type dependent gene expression programs. The inner nuclear membrane protein emerin has been implicated in regulating global chromatin architecture. We show emerin associates with genomic loci of muscle differentiation promoting factors in murine myogenic progenitors, including Myf5 and MyoD. Prior to their transcriptional activation Myf5 and MyoD loci localized to the nuclear lamina in proliferating progenitors and moved to the nucleoplasm upon transcriptional activation during differentiation. The Pax7 locus, which is transcribed in proliferating progenitors, localized to the nucleoplasm and Pax7 moved to the nuclear lamina upon repression during differentiation. Localization of Myf5, MyoD, and Pax7 to the nuclear lamina and proper temporal expression of these genes required emerin and HDAC3. Interestingly, activation of HDAC3 catalytic activity rescued both Myf5 localization to the nuclear lamina and its expression. Collectively, these data support a model whereby emerin facilitates repressive chromatin formation at the nuclear lamina by activating the catalytic activity of HDAC3 to regulate the coordinated spatiotemporal expression of myogenic differentiation genes.
Department of Medicine, Section of Cardiology, The University of Chicago, 5841 S. Maryland Ave, MC6088, Rm A607, Chicago, IL, 60637, USA, demmerle@uchicago.edu.
Justin
J
Demmerle
Adam J
AJ
Koch
James M
JM
Holaska
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000099186:Histone Deacetylase 3
D002843:Chromatin; D006655:Histone Deacetylases; D008565:Membrane Proteins; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D009687:Nuclear Proteins; D051763:PAX7 Transcription Factor; D000099186:Histone Deacetylase 3; C497418:Myf5 protein, mouse; C057363:MyoD1 myogenic differentiation protein; C497322:Pax7 protein, mouse; C092710:emerin