title: Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in  Neural Stem Cells and In Vivo Reprogramming.
abstract: The 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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Derek K
authors.initials: DK
authors.lastname: Smith
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Wenze
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Sanhua
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Nida
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: Department of Neurosciences, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Neurosciences, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: chun-li.zhang@utsouthwestern.edu.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D065150:Cellular Reprogramming; D003342:Corpus Striatum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C489726:Myt1 protein, mouse; C490258:Nr2e1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors