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Muscle-relevant genes marked by stable H3K4me2/3 profiles and enriched MyoD binding during myogenic differentiation

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Item Type:Article
Title:Muscle-relevant genes marked by stable H3K4me2/3 profiles and enriched MyoD binding during myogenic differentiation
Creators Name:Cui, H., Bansal, V., Grunert, M., Malecova, B., Dall Agnese, A., Latella, L., Gatto, S., Ryan, T., Schulz, K., Chen, W., Dorn, C., Puri, P.L. and Sperling, S.R.
Abstract:Post-translational modifications of histones play a key role in the regulation of gene expression during development and differentiation. Numerous studies have shown the dynamics of combinatorial regulation by transcription factors and histone modifications, in the sense that different combinations lead to distinct expression outcomes. Here, we investigated gene regulation by stable enrichment patterns of histone marks H3K4me2 and H3K4me3 in combination with the chromatin binding of the muscle tissue-specific transcription factor MyoD during myogenic differentiation of C2C12 cells. Using k-means clustering, we found that specific combinations of H3K4me2/3 profiles over and towards the gene body impact on gene expression and marks a subset of genes important for muscle development and differentiation. By further analysis, we found that the muscle key regulator MyoD was significantly enriched on this subset of genes and played a repressive role during myogenic differentiation. Among these genes, we identified the pluripotency gene Patz1, which is repressed during myogenic differentiation through direct binding of MyoD to promoter elements. These results point to the importance of integrating histone modifications and MyoD chromatin binding for coordinated gene activation and repression during myogenic differentiation.
Keywords:Cell Differentiation, Cell Line, Cultured Cells, Cluster Analysis, Fibroblasts, Gene Expression Profiling, Gene Ontology, HEK293 Cells, Histones, Lysine, Methylation, Muscle Development, MyoD Protein, Myoblasts, Neoplasm Proteins, Protein Binding, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science
Volume:12
Number:6
Page Range:e0179464
Date:13 June 2017
Official Publication:https://doi.org/10.1371/journal.pone.0179464
PubMed:View item in PubMed

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