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PCAF Involvement in Lamin A/C-HDAC2 Interplay during the Early Phase of Muscle Differentiation.
- Source :
-
Cells [Cells] 2020 Jul 20; Vol. 9 (7). Date of Electronic Publication: 2020 Jul 20. - Publication Year :
- 2020
-
Abstract
- Lamin A/C has been implicated in the epigenetic regulation of muscle gene expression through dynamic interaction with chromatin domains and epigenetic enzymes. We previously showed that lamin A/C interacts with histone deacetylase 2 (HDAC2). In this study, we deepened the relevance and regulation of lamin A/C-HDAC2 interaction in human muscle cells. We present evidence that HDAC2 binding to lamina A/C is related to HDAC2 acetylation on lysine 75 and expression of p300-CBP associated factor (PCAF), an acetyltransferase known to acetylate HDAC2. Our findings show that lamin A and farnesylated prelamin A promote PCAF recruitment to the nuclear lamina and lamin A/C binding in human myoblasts committed to myogenic differentiation, while protein interaction is decreased in differentiating myotubes. Interestingly, PCAF translocation to the nuclear envelope, as well as lamin A/C-PCAF interaction, are reduced by transient expression of lamin A mutated forms causing Emery Dreifuss muscular dystrophy. Consistent with this observation, lamin A/C interaction with both PCAF and HDAC2 is significantly reduced in Emery-Dreifuss muscular dystrophy myoblasts. Overall, these results support the view that, by recruiting PCAF and HDAC2 in a molecular platform, lamin A/C might contribute to regulate their epigenetic activity required in the early phase of muscle differentiation.
- Subjects :
- Animals
HEK293 Cells
Humans
Lamin Type A genetics
Mice
Models, Biological
Muscular Dystrophy, Emery-Dreifuss genetics
Muscular Dystrophy, Emery-Dreifuss pathology
Mutation genetics
Nuclear Lamina metabolism
Phenotype
Protein Binding
Cell Differentiation
Histone Deacetylase 2 metabolism
Lamin Type A metabolism
Muscles cytology
p300-CBP Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 9
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 32698523
- Full Text :
- https://doi.org/10.3390/cells9071735