کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2093753 1081976 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming
چکیده انگلیسی


• An evolutionarily conserved enhancer drives Tlx expression in neural stem cells
• SOX2 directly activates the identified enhancer and Tlx expression
• SOX2-mediated in vivo reprogramming of astrocytes to neuroblasts requires TLX

SummaryThe orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 5, Issue 5, 10 November 2015, Pages 805–815
نویسندگان
, , , , , , , ,