Matches in SemOpenAlex for { <https://semopenalex.org/work/W4292634139> ?p ?o ?g. }
- W4292634139 endingPage "1936.e9" @default.
- W4292634139 startingPage "1922" @default.
- W4292634139 abstract "Sequence variants in cis-acting enhancers are important for polygenic disease, but their role in Mendelian disease is poorly understood. Redundancy between enhancers that regulate the same gene is thought to mitigate the pathogenic impact of enhancer mutations. Recent findings, however, have shown that loss-of-function mutations in a single enhancer near PTF1A cause pancreas agenesis and neonatal diabetes. Using mouse and human genetic models, we show that this enhancer activates an entire PTF1A enhancer cluster in early pancreatic multipotent progenitors. This leading role, therefore, precludes functional redundancy. We further demonstrate that transient expression of PTF1A in multipotent progenitors sets in motion an epigenetic cascade that is required for duct and endocrine differentiation. These findings shed insights into the genome regulatory mechanisms that drive pancreas differentiation. Furthermore, they reveal an enhancer that acts as a regulatory master key and is thus vulnerable to pathogenic loss-of-function mutations." @default.
- W4292634139 created "2022-08-22" @default.
- W4292634139 creator A5003942395 @default.
- W4292634139 creator A5004697708 @default.
- W4292634139 creator A5025084099 @default.
- W4292634139 creator A5026684297 @default.
- W4292634139 creator A5027639273 @default.
- W4292634139 creator A5037226224 @default.
- W4292634139 creator A5052815182 @default.
- W4292634139 creator A5054736043 @default.
- W4292634139 creator A5083614468 @default.
- W4292634139 creator A5091231317 @default.
- W4292634139 date "2022-08-01" @default.
- W4292634139 modified "2023-10-13" @default.
- W4292634139 title "Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster" @default.
- W4292634139 cites W1533644174 @default.
- W4292634139 cites W1568038787 @default.
- W4292634139 cites W1701211704 @default.
- W4292634139 cites W1859117663 @default.
- W4292634139 cites W1912312559 @default.
- W4292634139 cites W1971578941 @default.
- W4292634139 cites W1973556785 @default.
- W4292634139 cites W1973725287 @default.
- W4292634139 cites W1977426188 @default.
- W4292634139 cites W1980786543 @default.
- W4292634139 cites W1980797966 @default.
- W4292634139 cites W1980911974 @default.
- W4292634139 cites W1986085728 @default.
- W4292634139 cites W1988623932 @default.
- W4292634139 cites W1993055783 @default.
- W4292634139 cites W2010921681 @default.
- W4292634139 cites W2011710385 @default.
- W4292634139 cites W2014677321 @default.
- W4292634139 cites W2017400430 @default.
- W4292634139 cites W2030148675 @default.
- W4292634139 cites W2031959007 @default.
- W4292634139 cites W2032472678 @default.
- W4292634139 cites W2036897871 @default.
- W4292634139 cites W2045949302 @default.
- W4292634139 cites W2047997227 @default.
- W4292634139 cites W2055426186 @default.
- W4292634139 cites W2064847335 @default.
- W4292634139 cites W2071918482 @default.
- W4292634139 cites W2081528800 @default.
- W4292634139 cites W2089688272 @default.
- W4292634139 cites W2099540110 @default.
- W4292634139 cites W2100826819 @default.
- W4292634139 cites W2101033119 @default.
- W4292634139 cites W2102619694 @default.
- W4292634139 cites W2106530741 @default.
- W4292634139 cites W2108234281 @default.
- W4292634139 cites W2132117628 @default.
- W4292634139 cites W2136170142 @default.
- W4292634139 cites W2137987484 @default.
- W4292634139 cites W2144112229 @default.
- W4292634139 cites W2147871659 @default.
- W4292634139 cites W2155047427 @default.
- W4292634139 cites W2156490774 @default.
- W4292634139 cites W2156696529 @default.
- W4292634139 cites W2162822589 @default.
- W4292634139 cites W2164330963 @default.
- W4292634139 cites W2164956879 @default.
- W4292634139 cites W2170551349 @default.
- W4292634139 cites W2170830174 @default.
- W4292634139 cites W2171808845 @default.
- W4292634139 cites W2179438025 @default.
- W4292634139 cites W2194390873 @default.
- W4292634139 cites W2300774973 @default.
- W4292634139 cites W2460791617 @default.
- W4292634139 cites W2464000940 @default.
- W4292634139 cites W2576205103 @default.
- W4292634139 cites W2603000633 @default.
- W4292634139 cites W2608952290 @default.
- W4292634139 cites W2730493494 @default.
- W4292634139 cites W2756892964 @default.
- W4292634139 cites W2786174959 @default.
- W4292634139 cites W2800968671 @default.
- W4292634139 cites W2805619986 @default.
- W4292634139 cites W2899546454 @default.
- W4292634139 cites W2903543972 @default.
- W4292634139 cites W2935837958 @default.
- W4292634139 cites W2949177718 @default.
- W4292634139 cites W2954958768 @default.
- W4292634139 cites W2979981308 @default.
- W4292634139 cites W2996224374 @default.
- W4292634139 cites W2997946728 @default.
- W4292634139 cites W3010741834 @default.
- W4292634139 cites W3015127073 @default.
- W4292634139 cites W3037769443 @default.
- W4292634139 cites W3047447368 @default.
- W4292634139 cites W3083091457 @default.
- W4292634139 cites W3088385305 @default.
- W4292634139 cites W3099179344 @default.
- W4292634139 cites W3119327744 @default.
- W4292634139 cites W3120241853 @default.
- W4292634139 cites W3127286697 @default.
- W4292634139 cites W3131634425 @default.
- W4292634139 cites W3159317682 @default.