Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CRISPRi/a functional screen with PARP7 inhibitor in NCI-H1373 cells

ABSTRACT: PARP7 is a monoPARP that catalyzes the transfer of single units of ADP-ribose onto substrates to change their function. PARP7 expression is increased by aromatic hydrocarbons and cellular stress, and the PARP7 gene is amplified in cancers, especially in those of the upper aerodigestive tract. PARP7 is a negative regulator of nucleic acid sensing in tumor cells. Inhibition of PARP7 restores Type I IFN signaling responses to nucleic acids in tumor models. Restored signaling can directly inhibit cell proliferation and activate the immune system, both of which contribute to tumor regression. RBN-2397 is a potent and selective inhibitor of PARP7. To further explore how RBN-2397 inhibits NCI-H1373 cell proliferation, we performed unbiased genetic screens using whole-genome CRISPRi and CRISPRa libraries (le Sage et al., 2017; Jost and Weissman, 2018). Comparison of CRISPRi and CRISPRa phenotype scores highlights genes with opposing functionality upon RBN-2397 treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178386 | GEO | 2021/06/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional changes by PARP7 inhibitor in cancer cell lines

Project description:PARP7 is a monoPARP that catalyzes the transfer of single units of ADP-ribose onto substrates to change their function. PARP7 expression is increased by aromatic hydrocarbons and cellular stress, and the PARP7 gene is amplified in cancers, especially in those of the upper aerodigestive tract. PARP7 is a negative regulator of nucleic acid sensing in tumor cells. Inhibition of PARP7 restores Type I IFN signaling responses to nucleic acids in tumor models. Restored signaling can directly inhibit cell proliferation and activate the immune system, both of which contribute to tumor regression. RBN-2397 is a potent and selective inhibitor of PARP7. To further investigate the mechanism of action of RBN-2397 and identify potential biomarkers we investigated transcriptional changes after RBN-2397 treatment in two PARP7 inhibitor sensitive cell lines, NCI-H1373 and NCI-H647, by RNA sequencing.

2021-06-13 | GSE177494 | GEO

Jurkat CRISPRi ATAC-seq [Series 3]

Project description:We develop a system for bidirectional epigenetic editing (CRISPRai), in which orthogonal activating (CRISPRa) and repressive (CRISPRi) perturbations are applied simultaneously to multiple loci the same cell. We perform ATAC-seq on CRISPRi perturbed Jurkat T cells to investigate chromatin accessibility changes upon perturbation of individual regulatory elements.

2024-03-16 | GSE261695 | GEO

Transcriptional changes by RBN-2397 treatment and FRA1 knockdown in NCI-H1975 cells

Project description:PARP7 inhibitors reduce tumor growth in a cell-autonomous manner and by enhancing immune recognition through restoring nucleic acid (NA)-sensing-dependent innate immune signaling. However, the molecular targets of PARP7-mediated ADP-ribosylation, regulating cell survival and innate immune signaling, remained elusive. Here, we identified PARP7 as a nuclear and cysteine-specific mono-ART that ADP-ribosylates proteins critical for regulating gene expression, such as the AP-1 transcription factor FRA1. Upon PARP7 inhibition the loss of FRA1 ADP-ribosylation increased FRA1 degradation in a PSMC3 and proteasomal-dependent manner. To further investigate how FRA1 promotes cell survival, we investigated transcriptional changes after RBN-2397 treatment and FRA1 knockdown in the PARP7 inhibitor sensitive cell line NCI-H1975 by RNA sequencing.

2023-12-06 | GSE229674 | GEO

CRISPR-based epigenome editing screens identify transcriptional and epigenetic regulators of human CD8 T cell function [CRISPRi/a TF scRNA-seq characterization]

Project description:Human CD8+CCR7+ T cells from three donors were transduced with CRISPRi and CRISPRa TF gRNA libraries and expanded for 10 days. After 10 days, we used single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic effects of silencing or activating each gene candidate.

2023-05-24 | GSE218985 | GEO

RNA-seq of CSMD1 enhancer CRISPRi in LUHMES cells and differentiated neurons

Project description:we performed lentiviral CRISPR interference (CRISPRi) by recruiting dCas9 fused with the KRAB domain to the CSMD1 enhancer (fam3) in the neuronal precursor cell line – Lund human mesencephalic (LUHMES). Given that the expression of CSMD1 was not detectable in LUHMES cells we differentiated these cells into neurons. Differentiated neurons with CRISPRi of CSMD1 enhancer showed significantly higher expression of CSMD1 than control.

2022-06-30 | E-MTAB-8027 | biostudies-arrayexpress

Mass spectrometric profiling of lysine malonylation in CRISPRi 562 cells lines to investigate malonylation activity of lysine acetyltransferases

Project description:Lysine malonylation is a protein posttranslational modification with potentially broad biological impact. We present a protocol to generate stable gene knockdown K562 cell lines through lentiviral infection of a CRISPRi system followed by lysine malonylation measurement using mass spectrometry (MS). We detail gRNA vector cloning, lentiviral infection, cell line purification, protein digestion, malonyllysine enrichment, desalting, and MS acquisition and analysis. This protocol can be applied for CRISPRa cell line generation and lysine malonylation profiling in tissues, with slight changes.

2023-12-04 | MSV000093564 | MassIVE

iPSC RNA-seq upon CRISPRn or CRISPRi manipulation

Project description:Assess the on- and off-target effects of dox-inducible CRISPR/Cas9 and CRISPRi constructs in a human iPS cell line. Transcript quantification of 3 cell lines, each plus or minus doxycycline and with or without specific single guide RNAs (sgRNAs), with 2 biological replicates each.

2016-01-19 | E-GEOD-76980 | biostudies-arrayexpress

CRISPR-based epigenome editing screens identify transcriptional and epigenetic regulators of human CD8 T cell function [Sorting-based CRISPR screens]

Project description:All bulk CRISPR based screens CD2 and B2M CRISPRi tiling screens (primary human CD8 T cells), IL2RA CRISPRa tiling screens (Jurkats), CRISPRi/a TF screens (primary human CD8 T cells), and CRISPR TFome KO (primary human T cells)

2023-08-31 | GSE241933 | GEO

CRISPRi screen of prostate cancer associated risk cis-regulatory elements [CRISPRi]

Project description:CRISPRi screen of prostate cancer associated risk cis-regulatory elements [CRISPRi]

| PRJNA598432 | ENA

CRISPRi/a functional screen with PARP7 inhibitor in NCI-H1373 cells

Project description:CRISPRi/a functional screen with PARP7 inhibitor in NCI-H1373 cells

| PRJNA738855 | ENA