FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4319455731> ?p ?o ?g. }

• W4319455731 endingPage "1246" @default.
• W4319455731 startingPage "1219" @default.
• W4319455731 abstract "Loss of AT-rich interactive domain-containing protein 1A (ARID1A) fosters acinar-to-ductal metaplasia (ADM) and pancreatic carcinogenesis by down-regulating transcription programs controlling acinar cell identity. However, how ARID1A reacts to metaplasia-triggering environmental cues remains elusive. Here, we aimed to elucidate the role of ARID1A in controlling ductal pancreatic gene signatures and deciphering hierarchical signaling cues determining ARID1A-dependent chromatin regulation during acinar cell reprogramming.Acinar cell explants with differential ARID1A status were subjected to genome-wide expression analyses. The impact of epidermal growth factor receptor (EGFR) signaling, NFATc1 activity, and ARID1A status on acinar reprogramming processes were characterized by ex vivo ADM assays and transgenic mouse models. EGFR-dependent ARID1A chromatin binding was studied by chromatin immunoprecipitation sequencing analysis and cellular fractionation.EGFR signaling interferes with ARID1A-dependent transcription by inducing genome-wide ARID1A displacement, thereby phenocopying ARID1A loss-of-function mutations and inducing a shift toward ADM permissive ductal transcription programs. Moreover, we show that EGFR signaling is required to push ARID1A-deficient acinar cells toward a metaplastic phenotype. Mechanistically, we identified the transcription factor nuclear factor of activated T cells 1 (NFATc1) as the central regulatory hub mediating both EGFR signaling-induced genomic ARID1A displacement and the induction of ADM-promoting gene signatures in the absence of ARID1A. Consequently, pharmacologic inhibition of NFATc1 or its depletion in transgenic mice not only preserves genome-wide ARID1A occupancy, but also attenuates acinar metaplasia led by ARID1A loss.Our data describe an intimate relationship between environmental signaling and chromatin remodeling in orchestrating cell fate decisions in the pancreas, and illustrate how ARID1A loss influences transcriptional regulation in acinar cell reprogramming." @default.
• W4319455731 created "2023-02-09" @default.
• W4319455731 creator A5006822602 @default.
• W4319455731 creator A5014477435 @default.
• W4319455731 creator A5018404918 @default.
• W4319455731 creator A5026125772 @default.
• W4319455731 creator A5028676156 @default.
• W4319455731 creator A5034261723 @default.
• W4319455731 creator A5040773420 @default.
• W4319455731 creator A5044355879 @default.
• W4319455731 creator A5045288328 @default.
• W4319455731 creator A5046422102 @default.
• W4319455731 creator A5055388147 @default.
• W4319455731 creator A5059210191 @default.
• W4319455731 creator A5077558876 @default.
• W4319455731 creator A5087245575 @default.
• W4319455731 creator A5089603081 @default.
• W4319455731 date "2023-01-01" @default.
• W4319455731 modified "2023-10-16" @default.
• W4319455731 title "NFATc1 Is a Central Mediator of EGFR-Induced ARID1A Chromatin Dissociation During Acinar Cell Reprogramming" @default.
• W4319455731 cites W1480548208 @default.
• W4319455731 cites W1965462878 @default.
• W4319455731 cites W1969201526 @default.
• W4319455731 cites W1970847274 @default.
• W4319455731 cites W1974869516 @default.
• W4319455731 cites W1978664503 @default.
• W4319455731 cites W1982781304 @default.
• W4319455731 cites W1993913862 @default.
• W4319455731 cites W2010916968 @default.
• W4319455731 cites W2022237004 @default.
• W4319455731 cites W2029572679 @default.
• W4319455731 cites W2041746655 @default.
• W4319455731 cites W2043346845 @default.
• W4319455731 cites W2056646351 @default.
• W4319455731 cites W2058836507 @default.
• W4319455731 cites W2063815548 @default.
• W4319455731 cites W2066034477 @default.
• W4319455731 cites W2066135299 @default.
• W4319455731 cites W2066650952 @default.
• W4319455731 cites W2071607446 @default.
• W4319455731 cites W2073229191 @default.
• W4319455731 cites W2076415441 @default.
• W4319455731 cites W2080832893 @default.
• W4319455731 cites W2087276195 @default.
• W4319455731 cites W2095934571 @default.
• W4319455731 cites W2108234281 @default.
• W4319455731 cites W2112350662 @default.
• W4319455731 cites W2124985265 @default.
• W4319455731 cites W2129140055 @default.
• W4319455731 cites W2134526812 @default.
• W4319455731 cites W2136411119 @default.
• W4319455731 cites W2139745007 @default.
• W4319455731 cites W2140729960 @default.
• W4319455731 cites W2141458291 @default.
• W4319455731 cites W2148261329 @default.
• W4319455731 cites W2154229063 @default.
• W4319455731 cites W2157665070 @default.
• W4319455731 cites W2163958696 @default.
• W4319455731 cites W2165793228 @default.
• W4319455731 cites W2169456326 @default.
• W4319455731 cites W2171808845 @default.
• W4319455731 cites W2171987817 @default.
• W4319455731 cites W2179438025 @default.
• W4319455731 cites W2274957308 @default.
• W4319455731 cites W2309167097 @default.
• W4319455731 cites W2346143774 @default.
• W4319455731 cites W2405696064 @default.
• W4319455731 cites W2521982858 @default.
• W4319455731 cites W2526262591 @default.
• W4319455731 cites W2566901884 @default.
• W4319455731 cites W2574440519 @default.
• W4319455731 cites W2586526035 @default.
• W4319455731 cites W2591968025 @default.
• W4319455731 cites W2594353026 @default.
• W4319455731 cites W2748710555 @default.
• W4319455731 cites W2791679730 @default.
• W4319455731 cites W2794844550 @default.
• W4319455731 cites W2883052135 @default.
• W4319455731 cites W2884301770 @default.
• W4319455731 cites W2890029692 @default.
• W4319455731 cites W2896987809 @default.
• W4319455731 cites W2936366750 @default.
• W4319455731 cites W2939121528 @default.
• W4319455731 cites W2940639077 @default.
• W4319455731 cites W2942918459 @default.
• W4319455731 cites W2948380101 @default.
• W4319455731 cites W2949636912 @default.
• W4319455731 cites W2964097765 @default.
• W4319455731 cites W2964615569 @default.
• W4319455731 cites W2967087236 @default.
• W4319455731 cites W2971573586 @default.
• W4319455731 cites W2996178726 @default.
• W4319455731 cites W2997876997 @default.
• W4319455731 cites W3019483263 @default.
• W4319455731 cites W3084414277 @default.
• W4319455731 cites W3087468412 @default.
• W4319455731 cites W3101617773 @default.
• W4319455731 doi "https://doi.org/10.1016/j.jcmgh.2023.01.015" @default.

• next