| Autor: |
Jason T Lambert, Linda Su-Feher, Karol Cichewicz, Tracy L Warren, Iva Zdilar, Yurong Wang, Kenneth J Lim, Jessica L Haigh, Sarah J Morse, Cesar P Canales, Tyler W Stradleigh, Erika Castillo Palacios, Viktoria Haghani, Spencer D Moss, Hannah Parolini, Diana Quintero, Diwash Shrestha, Daniel Vogt, Leah C Byrne, Alex S Nord |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.69479 |
| Popis: |
Enhancers are cis-regulatory elements that play critical regulatory roles in modulating developmental transcription programs and driving cell-type-specific and context-dependent gene expression in the brain. The development of massively parallel reporter assays (MPRAs) has enabled high-throughput functional screening of candidate DNA sequences for enhancer activity. Tissue-specific screening of in vivo enhancer function at scale has the potential to greatly expand our understanding of the role of non-coding sequences in development, evolution, and disease. Here, we adapted a self-transcribing regulatory element MPRA strategy for delivery to early postnatal mouse brain via recombinant adeno-associated virus (rAAV). We identified and validated putative enhancers capable of driving reporter gene expression in mouse forebrain, including regulatory elements within an intronic CACNA1C linkage disequilibrium block associated with risk in neuropsychiatric disorder genetic studies. Paired screening and single enhancer in vivo functional testing, as we show here, represents a powerful approach towards characterizing regulatory activity of enhancers and understanding how enhancer sequences organize gene expression in the brain. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
