Abstract
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.
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Abbreviations
- ChIP:
-
Chromatin immunoprecipitation
- ESCs:
-
Embryonic stem cells
- FISH:
-
Fluorescent in situ hybridization
- HDAC3:
-
Histone deacetylase 3
- INM:
-
Inner nuclear membrane
- LAD:
-
Lamina-associated domain
- LASs:
-
Lamina-associated sequences
- LBR:
-
Lamin B receptor
- Myf5:
-
Myogenic factor 5
- MyoD:
-
Myoblast determination protein 1
- NCoR:
-
Nuclear corepressor complex
- NPC:
-
Nuclear pore complex
- ONM:
-
Outer nuclear membrane
- Pax3:
-
Paired box 3
- Pax7:
-
Paired box 7
- PRC2:
-
Polycomb repressive complex 2
- X-EDMD:
-
X-linked Emery–Dreifuss muscular dystrophy
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Acknowledgments
We thank Harinder Singh, Ignacio Demarco, Joseph Zullo, and Eric Bertolino for assistance with 3D DNA-ImmunoFISH and reagents; Christine Labno at the University of Chicago Light Microscopy Core for valuable guidance with image acquisition and processing; and Aaron Mull of the Holaska lab for experimental help. This work was supported by the Ellison Medical Foundation (J.M.H. and J.D.) and the National Institutes of Health (T32 GM007197 and T32 HL007381, A.J.K.).
Ethical Standards Statement
These experiments comply with the current laws for ethical conduct in the USA. This article does not contain any studies with human or animal subjects performed by any of the authors.
Competing Interests
Justin Demmerle, Adam J Koch, and James M Holaska declare no competing interests.
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Demmerle, J., Koch, A.J. & Holaska, J.M. Emerin and histone deacetylase 3 (HDAC3) cooperatively regulate expression and nuclear positions of MyoD, Myf5, and Pax7 genes during myogenesis. Chromosome Res 21, 765–779 (2013). https://doi.org/10.1007/s10577-013-9381-9
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DOI: https://doi.org/10.1007/s10577-013-9381-9