SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol

Mathies, Laura D.; Lindsay, Jonathan H.; Handal, Amal P.; Blackwell, GinaMari G.; Davies, Andrew G.; Bettinger, Jill C.

doi:10.1186/s12864-020-07059-y

Cited by 9 publications

(8 citation statements)

References 68 publications

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“…Interestingly, CREBBP at risk locus chr16:3606788-4606788, which scored in 2D, 3D and in vivo screens as a tumor-suppressor gene, was strongly connected with the same cluster suggesting that CREBBP regulates the SWI/SNF complex. This is consistent with previous reports of CREBBP function 47,48 . Furthermore, in agreement with the results described above, we found that DUSP4 has an expression signature similar to components of the MAPK signaling pathway.…”

Section: Survival Analysis In Cancer Patients Confirms Directionality and Cancer Association Of Bc Risk Genessupporting

confidence: 94%

CRISPR screens identify gene targets and drug repositioning opportunities at breast cancer risk loci

Rosenbluh

Tuano

Milne

et al. 2022

Preprint

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Genome-wide association studies (GWAS) have identified >200 loci associated with breast cancer (BC) risk. The majority of candidate causal variants (CCVs) are in non-coding regions and likely modulate cancer risk by regulating gene expression. However, pinpointing the exact target of the association and identifying the phenotype it mediates is a major challenge in the interpretation and translation of GWAS. Here, we used pooled CRISPR activation and suppression screens to evaluate predicted GWAS target genes, and to define the cancer phenotypes they mediate. We measured proliferation in 2D, 3D, and in immune-deficient mice, as well as the effect on DNA repair. We performed 60 CRISPR screens and identified 21 genes predicted with high confidence to be GWAS targets that drive a cancer phenotype by driving a proliferation or DNA damage response in breast cells. We validated the regulation of a subset of these genes by BC-risk variants, and show the utility of expression profiling for drug repurposing. We provide a platform for identifying gene targets of risk variants, and present a blueprint of interventions for BC risk reduction and treatment.

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Section: Survival Analysis In Cancer Patients Confirms Directionality and Cancer Association Of Bc Risk Genessupporting

confidence: 94%

CRISPR screens identify gene targets and drug repositioning opportunities at breast cancer risk loci

Rosenbluh

Tuano

Milne

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Interestingly, CREBBP at risk locus chr16:3606788-4606788, which scored in 2D, 3D and in vivo screens as a tumor-suppressor gene, was strongly connected with the same cluster suggesting that CREBBP regulates the SWI/SNF complex. This is consistent with previous reports of CREBBP function (Alver et al, 2017;Mathies et al, 2020). Furthermore, in agreement with the results described above, we found that DUSP4 has an expression signature similar to components of the MAPK signaling pathway.…”

Section: Hichip and Crisprqtl Validate Distal Regulation Between Bc Risk Loci And Genessupporting

confidence: 93%

CRISPR screens identify gene targets and drug repositioning opportunities at breast cancer risk loci

Tuano

Beesley

Manning

et al. 2021

Preprint

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Genome-wide association studies (GWAS) have identified >200 loci associated with breast cancer (BC) risk. The majority of candidate causal variants (CCVs) are in non-coding regions and are likely to modulate cancer risk by regulating gene expression. We recently developed a scoring system, INQUISIT, to predict candidate risk genes at BC-risk loci. Here, we used pooled CRISPR activation and suppression screens to validate INQUISIT predictions, and to define the cancer phenotypes they mediate. We measured proliferation in 2D, 3D, and in immune-deficient mice, as well as the effect on the DNA damage response. We performed 60 CRISPR screens and identified 21 high-confidence INQUISIT predictions that mediate a cancer phenotype. We validated the direct regulation of a subset of genes by BC-risk variants using HiCHIP and CRISPRqtl. Furthermore, we show the utility of expression profiling for drug repurposing against these targets. We provide a platform for identifying gene targets of risk variants, and lay a blueprint of interventions for BC risk reduction and treatment.

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“…3, E and F). cbp-1 encodes the C. elegans ortholog of histone acetyltransferase p300/CBP that promotes gene transcription (35)(36)(37)(38)(39)(40)(41)(42)(43). RNAi against many of the known genes encoding heat-responding transcription factor, including hsf-1, hsf-2, hif-1, and nhr-49, did not block TSP-1::GFP up-regulation (table S1).…”

Section: Resultsmentioning

confidence: 99%

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin

Jiang,

De Belly,

Wang

et al. 2024

Sci. Adv.

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Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here, we show that early-life thermal stress strongly up-regulates tsp-1 , a gene encoding the conserved transmembrane tetraspanin in C. elegans . TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. Increased TSP-1 abundance persists even after transient early-life heat stress. Such regulation requires CBP-1, a histone acetyltransferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers marked C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity.

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SWI/SNF complexes act through CBP-1 histone acetyltransferase to regulate acute functional tolerance to alcohol

Cited by 9 publications

References 68 publications

CRISPR screens identify gene targets and drug repositioning opportunities at breast cancer risk loci

CRISPR screens identify gene targets and drug repositioning opportunities at breast cancer risk loci

CRISPR screens identify gene targets and drug repositioning opportunities at breast cancer risk loci

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin

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