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Transcription-Associated R-Loop Formation across the Human FMR1 CGG-Repeat Region
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نویسنده
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loomis e.w. ,sanz l.a. ,chédin f. ,hagerman p.j.
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منبع
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plos genetics - 2014 - دوره : 10 - شماره : 4
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چکیده
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Expansion of a trinucleotide (cgg) repeat element within the 5′ untranslated region (5′utr) of the human fmr1 gene is responsible for a number of heritable disorders operating through distinct pathogenic mechanisms: gene silencing for fragile x syndrome (>200 cgg) and rna toxic gain-of-function for fxtas (∼55-200 cgg). existing models have focused almost exclusively on post-transcriptional mechanisms,but co-transcriptional processes could also contribute to the molecular dysfunction of fmr1. we have observed that transcription through the gc-rich fmr1 5′utr region favors r-loop formation,with the nascent (g-rich) rna forming a stable rna:dna hybrid with the template dna strand,thereby displacing the non-template dna strand. using dna:rna (hybrid) immunoprecipitation (drip) of genomic dna from cultured human dermal fibroblasts with both normal (∼30 cgg repeats) and premutation (55
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آدرس
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department of biochemistry and molecular medicine,university of california,davis,school of medicine,davis,ca, United States, department of molecular and cellular biology,university of california,davis,davis,ca,united states,the genome center,university of california,davis,davis,ca, United States, department of molecular and cellular biology,university of california,davis,davis,ca,united states,the genome center,university of california,davis,davis,ca, United States, department of biochemistry and molecular medicine,university of california,davis,school of medicine,davis,ca,united states,mind institute,university of california,davis,health system,sacramento,ca, United States
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Authors
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