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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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A bivalent chromatin structure marks key developmental genes in embryonic stem cells
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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Hemming, S., Cakouros, D., Isenmann, S., Cooper, L., Menicanin, D., Zannettino, A., & Gronthos, S. (2014) · Stem Cells · doi:10.1002/stem.1573 · Cited by 259
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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