Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity
| العنوان: | Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity |
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| المؤلفون: | Adam G. West, Alan Hair, Carol Heath, Meiji Kit-Wan Ma |
| المصدر: | PLoS Genetics, Vol 7, Iss 7, p e1002175 (2011) Scopus-Elsevier PLoS Genetics |
| بيانات النشر: | Public Library of Science, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Cancer Research, Gene Expression, Chick Embryo, beta-Globins, Regulatory Sequences, Nucleic Acid, Histones, 0302 clinical medicine, Heterochromatin, Histone code, Genetics (clinical), Genetics, Regulation of gene expression, 0303 health sciences, Chromosome Biology, Histone Modification, Acetylation, Genomics, Chromatin, Cell biology, Histone Code, Histone, Epigenetics, Insulator Elements, RNA Interference, RNA Polymerase II, Research Article, Protein Binding, Chromosome Structure and Function, lcsh:QH426-470, Ubiquitin-Protein Ligases, Blotting, Western, Molecular Sequence Data, Biology, Methylation, Chromatin remodeling, Avian Proteins, 03 medical and health sciences, Cell Line, Tumor, Animals, Folate Receptor 1, Amino Acid Sequence, Molecular Biology, Ecology, Evolution, Behavior and Systematics, ChIA-PET, 030304 developmental biology, Sequence Homology, Amino Acid, Lysine, Ubiquitination, lcsh:Genetics, biology.protein, Heterochromatin protein 1, Chickens, 030217 neurology & neurosurgery |
| الوصف: | Genomic maps of chromatin modifications have provided evidence for the partitioning of genomes into domains of distinct chromatin states, which assist coordinated gene regulation. The maintenance of chromatin domain integrity can require the setting of boundaries. The HS4 insulator element marks the 3′ boundary of a heterochromatin region located upstream of the chicken β-globin gene cluster. Here we show that HS4 recruits the E3 ligase RNF20/BRE1A to mediate H2B mono-ubiquitination (H2Bub1) at this insulator. Knockdown experiments show that RNF20 is required for H2Bub1 and processive H3K4 methylation. Depletion of RNF20 results in a collapse of the active histone modification signature at the HS4 chromatin boundary, where H2Bub1, H3K4 methylation, and hyperacetylation of H3, H4, and H2A.Z are rapidly lost. A remarkably similar set of events occurs at the HSA/HSB regulatory elements of the FOLR1 gene, which mark the 5′ boundary of the same heterochromatin region. We find that persistent H2Bub1 at the HSA/HSB and HS4 elements is required for chromatin boundary integrity. The loss of boundary function leads to the sequential spreading of H3K9me2, H3K9me3, and H4K20me3 over the entire 50 kb FOLR1 and β-globin region and silencing of FOLR1 expression. These findings show that the HSA/HSB and HS4 boundary elements direct a cascade of active histone modifications that defend the FOLR1 and β-globin gene loci from the pervasive encroachment of an adjacent heterochromatin domain. We propose that many gene loci employ H2Bub1-dependent boundaries to prevent heterochromatin spreading. Author Summary The transcription of genes in eukaryotes occurs within the context of chromatin, a complex of DNA, histone proteins, and regulatory factors. Whole-genome profiling of chromatin proteins and histones that are post-translationally modified has revealed that genomes are organized into domains of distinct chromatin states that coordinate gene regulation. The integrity of chromatin domains can require the setting of their boundaries. DNA sequences known as chromatin insulator or boundary elements can establish boundaries between transcriptionally permissive and repressive chromatin domains. We have studied two chromatin boundary elements that flank a condensed chromatin region located between the chicken FOLR1 and β-globin genes, respectively. These elements recruit enzymes that mediate the ubiquitination of histone H2B. Histone H2B ubiquitination directs a cascade of so-called “active” histone modification events that favor chromatin accessibility. We observe a striking collapse of the active histone modification signature at both chromatin boundaries following the depletion of ubiquitinated H2B. This loss of boundary function leads to the comprehensive spreading of repressive chromatin over the entire FOLR1 and β-globin gene region, resulting in gene silencing. We propose that chromatin boundaries at many gene loci employ H2B ubiquitination to restrict the encroachment of repressive chromatin. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1553-7390 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::06dc6f8f4f0f88c31a188d031cb3dfc0 https://eprints.gla.ac.uk/54321/1/ID54321.pdf |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....06dc6f8f4f0f88c31a188d031cb3dfc0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537390 |
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