کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2119519 1085398 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sequence and epigenetic determinants in the regulation of the Math6 gene by Neurogenin3
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Sequence and epigenetic determinants in the regulation of the Math6 gene by Neurogenin3
چکیده انگلیسی

The bHLH factor Neurogenin3 initiates the differentiation program that leads to formation of pancreatic endocrine cells. Math6 is a closely related bHLH factor transiently activated downstream of Neurogenin3 in endocrine progenitors. Here we characterize the Math6 promoter and locate the Neurogenin3 binding site, thus confirming that Math6 is a genuine Neurogenin3 target. We also show that Math6 activation rates are largely controlled by epigenetic mechanisms involving the balance between activating H3K4 and repressive H3K27 methylation marks. High Math6 expression in the embryonic pancreas associates with an H3K4me3-only state, whereas low Math6 expression in differentiated endocrine cells correlates with chromatin dually marked with H3K4me3/H3K27me3, a feature originally associated with developmental genes that are repressed but poised for activation in ES cells. Importantly, we show that Neurogenin3 can trigger the conversion of Math6 from a poorly transcribed bivalent to an active monovalent state in vitro, hence providing a mechanism whereby Neurogenin3 may activate Math6 in endocrine progenitors. Finally, because Neurogenin3-induced changes in histone methylation are observed at other endocrine gene promoters, we propose that this mechanism may contribute to the determination of endocrine cell fate by Neurogenin3 in the pancreas.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Differentiation - Volume 82, Issue 2, September 2011, Pages 66–76
نویسندگان
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