RACK7 Senses and Fine-Tunes Enhancer Activity [Chromatin associated RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1189069 | ENA |
REPOSITORIES: ENA
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Project description:RACK7 Senses and Fine-Tunes Enhancer Activity [ChIP-Seq]
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Project description:RACK7 Senses and Fine-Tunes Enhancer Activity [TT-Seq]
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Project description:RACK7 senses enhancer activity changes and facilitates their activation
2025-05-26 | PXD058592 |
Project description:Enhancers regulate dynamic gene expression in a spatiotemporal specific manner. A number of positive as well as negative regulators of enhancers have been reported so far. However, whether and how these regulators sense enhancer activity dynamics remains unclear. In this study, we show that a specific enhancer regulator, RACK7, swiftly re-distributes from repressed enhancers to activated enhancers in response to a plethora of acute stimulations. We further show that this process depends on transcription and RACK7 positively regulates enhancer activation by promoting the recruitment of RNA polymerase II. Taken together, our findings suggest that RACK7 senses enhancer activity changes and facilitates their activation during acute stimulations.
2025-07-03 | GSE283270 | GEO
Project description:Enhancers regulate dynamic gene expression in a spatiotemporal specific manner. A number of positive as well as negative regulators of enhancers have been reported so far. However, whether and how these regulators sense enhancer activity dynamics remains unclear. In this study, we show that a specific enhancer regulator, RACK7, swiftly re-distributes from repressed enhancers to activated enhancers in response to a plethora of acute stimulations. We further show that this process depends on transcription and RACK7 positively regulates enhancer activation by promoting the recruitment of RNA polymerase II. Taken together, our findings suggest that RACK7 senses enhancer activity changes and facilitates their activation during acute stimulations.
2025-07-01 | GSE282268 | GEO
Project description:Enhancers regulate dynamic gene expression in a spatiotemporal specific manner. A number of positive as well as negative regulators of enhancers have been reported so far. However, whether and how these regulators sense enhancer activity dynamics remains unclear. In this study, we show that a specific enhancer regulator, RACK7, swiftly re-distributes from repressed enhancers to activated enhancers in response to a plethora of acute stimulations. We further show that this process depends on transcription and RACK7 positively regulates enhancer activation by promoting the recruitment of RNA polymerase II. Taken together, our findings suggest that RACK7 senses enhancer activity changes and facilitates their activation during acute stimulations.
2025-07-03 | GSE282513 | GEO
Project description:A human-specific enhancer fine-tunes radial glia potency and corticogenesis
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Project description:Humans evolved an extraordinarily expanded and complex cerebral cortex, associated with developmental and gene regulatory modifications1-3. Human accelerated regions (HARs) are highly conserved DNA sequences with human-specific nucleotide substitutions. Although there are thousands of annotated HARs, their functional contribution to species-specific cortical development is largely unknown4,5. HARE5 is a HAR transcriptional enhancer of the WNT signaling receptor Frizzled8 (FZD8) active during brain development6. Here, using genome-edited mouse and primate models, we demonstrate that human (Hs) HARE5 fine-tunes cortical development and connectivity by controlling the proliferative and neurogenic capacity of neural progenitor cells (NPCs). Hs-HARE5 knock-in mice have significantly enlarged neocortices, which contain more excitatory neurons. By measuring neural dynamics in vivo we show these anatomical features result in increased functional independence between cortical regions. To understand the underlying developmental mechanisms, we assess progenitor fate using fixed and live imaging, lineage analysis, and single-cell RNA sequencing. We discover Hs-HARE5 modifies radial glial progenitor behavior, with increased self-renewal at early developmental stages followed by expanded neurogenic potential later. We use genome-edited human and chimpanzee (Pt) NPCs and cortical organoids to assess the relative enhancer activity and function of Hs-HARE5 and Pt-HARE5. Using these orthogonal strategies we show four human-specific variants in HARE5 drive increased enhancer activity which promotes progenitor proliferation. Finally, we show that Hs-HARE5 promotes progenitor proliferation by increasing canonical WNT signaling. These findings illustrate how small changes in regulatory DNA can directly impact critical signaling pathways to modulate brain development. Our study uncovers new functions for HARs as key regulatory elements crucial for the expansion and complexity of the human cerebral cortex.
2025-03-06 | GSE287748 | GEO
Project description:Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes. Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer âbrakeâ to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. ChIP-seq data of RACK7, KDM5C and histone modifications in parental and RACK7-KO ZR-75-30 cells.
2016-04-07 | E-GEOD-71323 | biostudies-arrayexpress
Project description:Primed enhancers are marked by histone H3K4 mono-methylation (H3K4me1), and the conversion to active enhancers involves acetylation of histone H3K27 (H3K27Ac). However, whether active enhancers are regulated remains unclear. Here we report a biochemical complex consisting of a potential chromatin reader (RACK7) and a histone demethylase (KDM5C) that occupies many active enhancers in a breast cancer cell line. Loss of RACK7 or KDM5C results in hyperactive enhancers marked by H3K4me3 and H3K27Ac, and characterized by an increased eRNA transcription and elevated expression of nearby genes. Loss of RACK7 or KDM5C also leads to increased cell invasion and migration, and enhanced tumor growth. We propose that RACK7/KDM5C functions as an enhancer âbrakeâ to ensure appropriate enhancer activities in the cell. Our findings provide important insight into histone H3K4 methylation dynamics at enhancers and reveal a molecular mechanism that controls the activities of active enhancers, which when compromised, can contribute to tumorigenesis. ChIP-seq data of RACK7, KDM5C and histone modifications in parental and RACK7-KO ZR-75-30 cells.
2016-04-07 | E-GEOD-76637 | biostudies-arrayexpress