| 1. |
- Jain, Shruti, et al.
(författare)
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SnoRNA:U3:9B is required for the activation of immune response genes in Drosophila melanogaster
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Small nucleolar RNAs (snoRNAs) are prevailing components of the chromatin-associatedtranscriptome and many orphan snoRNAs are associated with protein coding genes in the genome ofDrosophila melanogaster. We have studied a specific chromatin-associated snoRNA, snoRNA:U3:9B,that binds to immune response genes. Using a Sindbis virus replicon model, we have shownthat snoRNA:U3:9B depletion in S2 cells leads to reduced immune response gene expression andreduced chromatin accessibility at target immune response genes. We have used CRISPR/Cas9 tocreate a snoRNA:U3:9B knock-out fly strain and revealed that snoRNA:U3:9B-deficient larvae areviable in control conditions, but fail to develop into pupae when challenged by expression of the Sindbisvirus replicon, which suggests that this snoRNA is essential for the activation of an effective antiviralresponse. In agreement with this proposal, the chromatin decompaction and gene activation normallyobserved at immune response gene loci in response to Sindbis replicon expression are abolished inthe snoRNA:U3:9B-deficient larvae, as shown by ATAC-qPCR and RT-qPCR analyses. Moreover,ChIRP-qPCR experiments have shown that snoRNA:U3:9B associates with the immune responsegenes in vivo, which suggests that the defects observed on chromatin compaction and gene expressionare due to direct regulatory events. In summary, our results reveal the existence of an epigeneticmechanism that requires snoRNA:U3:9B to modulate local chromatin accessibility and enable theinduction of immune response genes.
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| 2. |
- Regadas, Isabel, et al.
(författare)
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A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation
- 2021
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 81:8, s. 1766-1780
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Tidskriftsartikel (refereegranskat)abstract
- Organismal development and cell differentiation critically depend on chromatin state transitions. However, certain developmentally regulated genes lack histone 3 lysine 9 and 27 acetylation (H3K9ac and H3K27ac, respectively) and histone 3 lysine 4 (H3K4) methylation, histone modifications common to most active genes. Here we describe a chromatin state featuring unique histone 3 lysine 14 acetylation (H3K14ac) peaks in key tissue-specific genes in Drosophila and human cells. Replacing H3K14 in Drosophila demonstrates that H3K14 is essential for expression of genes devoid of canonical histone modifications in the embryonic gut and larval wing imaginal disc, causing lethality and defective wing patterning. We find that the SWI/SNF protein Brahma (Brm) recognizes H3K14ac, that brm acts in the same genetic pathway as H3K14R, and that chromatin accessibility at H3K14ac-unique genes is decreased in H3K14R mutants. Our results show that acetylation of a single lysine is essential at genes devoid of canonical histone marks and uncover an important requirement for H3K14 in tissue-specific gene regulation.
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| 3. |
- Tang, Min, et al.
(författare)
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Separation of transcriptional repressor and activator functions in Drosophila HDAC3
- 2023
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Ingår i: Development. - 0950-1991 .- 1477-9129. ; 150:15
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Tidskriftsartikel (refereegranskat)abstract
- The histone deacetylase HDAC3 is associated with the NCoR/SMRT co-repressor complex, and its canonical function is in transcriptional repression, but it can also activate transcription. Here, we show that the repressor and activator functions of HDAC3 can be genetically separated in Drosophila. A lysine substitution in the N terminus (K26A) disrupts its catalytic activity and activator function, whereas a combination of substitutions (HEBI) abrogating the interaction with SMRTER enhances repressor activity beyond wild type in the early embryo. We conclude that the crucial functions of HDAC3 in embryo development involve catalytic-dependent gene activation and non-enzymatic repression by several mechanisms, including tethering of loci to the nuclear periphery.
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