Arid1a controls tissue regeneration.
TL;DR: These studies implicate the SWI/SNF complexes are essential to embryonic development and tissue-specific differentiation.
Abstract: Switch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are crucial for regulating temporal and spatial gene expression during development (1). SWI/SNF
disrupts the DNA-histone interaction in an ATPase-dependent manner, alters the chromatin architecture and promotes a “poised” chromatin state (2,3). The poised state of chromatin makes it accessible for specific transcriptional regulators to facilitate tissue-specific gene expression profiles (4-6). SWI/SNF function is highly dependent on its subunit composition. Several SWI/SNF subunits, such as BAF155, BAF250a/b ( ARID1A/B ) and BRG1, are reported to affect self-renewal and differentiation in many tissues and embryonic stem (ES) cells (6-8). SWI/SNF complexes also increase transcriptional reprogramming efficiency during development (9). These studies implicate the SWI/SNF complexes are essential to embryonic development and tissue-specific differentiation.
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Laval University1, University of Oxford2, Boston Children's Hospital3, Westat4, University of California, San Diego5, Casa Sollievo della Sofferenza6, University of Milan7, Yale University8, National Institute for Health Research9, University of Bari10, University of Calgary11, National Institutes of Health12, Harvard University13, Catalan Institution for Research and Advanced Studies14, University of Manchester15
TL;DR: In this paper, a high-coverage whole-genome sequencing of 232 lung cancer in never smokers (LCINS) showed three subtypes defined by copy number aberrations.
Abstract: Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.
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