Department of Molecular, Cell, and Cancer Biology; Division of Cardiovascular Medicine, Department of Medicine; Department of Pediatrics, Division of Genes and Development; Rivera Lab; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Developmental Biology | Enzymes and Coenzymes | Genetic Phenomena
Regulation of chromatin structure is critical for cell type-specific gene expression. Many chromatin regulatory complexes exist in several different forms, due to alternative splicing and differential incorporation of accessory subunits. However, in vivo studies often utilize mutations that eliminate multiple forms of complexes, preventing assessment of the specific roles of each. Here we examined the developmental roles of the TIP55 isoform of the KAT5 histone acetyltransferase. In contrast to the pre-implantation lethal phenotype of mice lacking all four Kat5 transcripts, mice specifically deficient for Tip55 die around embryonic day 11.5 (E11.5). Prior to developmental arrest, defects in heart and neural tube were evident in Tip55 mutant embryos. Specification of cardiac and neural cell fates appeared normal in Tip55 mutants. However, cell division and survival were impaired in heart and neural tube, respectively, revealing a role for TIP55 in cellular proliferation. Consistent with these findings, transcriptome profiling revealed perturbations in genes that function in multiple cell types and developmental pathways. These findings show that Tip55 is dispensable for the pre- and early post-implantation roles of Kat5, but is essential during organogenesis. Our results raise the possibility that isoform-specific functions of other chromatin regulatory proteins may play important roles in development.
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© The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Sci Rep. 2018 Oct 8;8(1):14908. doi: 10.1038/s41598-018-33213-4. Link to article on publisher's site
Acharya D, Nera B, Milstone ZJ, Bourke L, Yoon Y, Rivera-Pérez JA, Trivedi CM, Fazzio TG. (2018). TIP55, a splice isoform of the KAT5 acetyltransferase, is essential for developmental gene regulation and organogenesis. Open Access Articles. https://doi.org/10.1038/s41598-018-33213-4. Retrieved from https://escholarship.umassmed.edu/oapubs/3633
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This work is licensed under a Creative Commons Attribution 4.0 License.