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UTX, a Histone H3-Lysine 27 Demethylase, Acts as a Critical Switch to Activate the Cardiac Developmental Program
Open accessAbstract
SUMMARY The removal of histone H3 lysine27 (H3K27) trimethylation mark is important for the robust induction of many cell type-specific genes during differentiation. Here we show that UTX, a H3K27 demethylase, acts as a critical switch to promote a cardiac-specific gene program. UTX-deficient ESCs failed to develop heart-like rhythmic contractions under a cardiac differentiation condition. UTX deficient mice show severe defects in heart development and embryonic lethality. We found that UTX is recruited to cardiac-specific enhancers by associating with core cardiac transcription factors and demethylates H3K27 residues in cardiac genes. In addition, UTX facilitates the recruitment of Brg1 to the cardiac-specific enhancers. Together, our data reveal key roles for UTX in a timely transition from poised to active chromatin in cardiac genes during heart development and a fundamental mechanism by which a H3K27 demethylase triggers tissue-specific chromatin changes.
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Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
A unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233
Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
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Whole-Genome Analysis of Histone H3 Lysine 4 and Lysine 27 Methylation in Human Embryonic Stem Cells
Pan, G., Tian, S., Nie, J., Yang, C., Ruotti, V., Wei, H., Jonsdottir, G. A., Stewart, R., & Thomson, J. A. (2007) · Cell Stem Cell · doi:10.1016/j.stem.2007.08.003 · Cited by 711
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X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner
Welstead, G. G., Creyghton, M. P., Bilodeau, S., Cheng, A. W., Markoulaki, S., Young, R. A., & Jaenisch, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210787109 · Cited by 194
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Denton, D., Aung-Htut, M. T., Lorensuhewa, N., Nicolson, S., Zhu, W., Mills, K., Cakouros, D., Bergmann, A., & Kumar, S. (2013) · Nature Communications · doi:10.1038/ncomms3916 · Cited by 58
Metadata
- Authors
- Lee, S., Lee, J. W., & Lee, S.-K.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 22
- Issue
- 1
- Pages
- 25-37
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2082430940
- Cited by
- 252
- References
- 5
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lee, S., Lee, J. W., & Lee, S.-K. (2012). UTX, a Histone H3-Lysine 27 Demethylase, Acts as a Critical Switch to Activate the Cardiac Developmental Program. Developmental Cell. https://doi.org/10.1016/j.devcel.2011.11.009
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