Drosophila histone demethylase KDM4A has enzymatic and non-enzymatic roles in controlling heterochromatin integrity
| Autor: | Sylvain V. Costes, Serafin U Colmenares, Cameron Kennedy, Gary H. Karpen, Joel M Swenson, Sasha A. Langley |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Euchromatin DNA Repair Transcription Genetic H3K56me3 Medical and Health Sciences Histones Double-Stranded position-effect variegation Heterochromatin Demethylase activity Drosophila Proteins DNA Breaks Double-Stranded Heterochromatin organization Genetics Histone Demethylases biology EZH2 Cell Cycle Position-effect variegation Biological Sciences Drosophila melanogaster Drosophila γH2Av dKDM4A Transcription 1.1 Normal biological development and functioning Methylation General Biochemistry Genetics and Molecular Biology Article Chromosomal Position Effects 03 medical and health sciences HP1a Genetic Protein Domains histone demethylase Underpinning research Animals Gene Silencing Molecular Biology Lysine DNA Breaks H3K36me3 fungi Cell Biology Cell Cycle Checkpoints 030104 developmental biology Fertility Gene Expression Regulation Mutation biology.protein Biocatalysis Demethylase Heterochromatin protein 1 Generic health relevance Developmental Biology |
| Zdroj: | Developmental cell, vol 42, iss 2 Colmenares, SU; Swenson, JM; Langley, SA; Kennedy, C; Costes, SV; & Karpen, GH. (2017). Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity. Developmental Cell, 42(2), 156-169.e5. doi: 10.1016/j.devcel.2017.06.014. Lawrence Berkeley National Laboratory: Retrieved from: http://www.escholarship.org/uc/item/06q8n6xh |
| Popis: | © 2017 Elsevier Inc. Eukaryotic genomes are broadly divided between gene-rich euchromatin and the highly repetitive heterochromatin domain, which is enriched for proteins critical for genome stability and transcriptional silencing. This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair. We demonstrate that dKDM4A demethylase activity is dispensable for PEV. In contrast, dKDM4A enzymatic activity is required to relocate heterochromatic double-strand breaks outside the domain, as well as for organismal survival when DNA repair is compromised. Finally, DNA damage triggers dKDM4A-dependent changes in the levels of H3K56me3, suggesting that dKDM4A demethylates this heterochromatic mark to facilitate repair. We conclude that dKDM4A, in addition to its previously characterized role in euchromatin, utilizes both enzymatic and structural mechanisms to regulate heterochromatin organization and functions. Colmenares et al. discover that Drosophila KDM4A, previously characterized as a euchromatic histone H3K36 demethylase and transcriptional regulator, is recruited to heterochromatin to contribute non-enzymatically to position-effect variegation, a hallmark of heterochromatin integrity. Conversely, dKDM4A catalytic activity is vital to heterochromatin DNA repair and is associated with demethylation of heterochromatic H3K56me3. |
| Databáze: | OpenAIRE |
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