Parallel functional testing identifies enhancers active in early postnatal mouse brain.

Autor:	Lambert JT; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Su-Feher L; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Cichewicz K; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Warren TL; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Zdilar I; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Wang Y; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Lim KJ; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Haigh JL; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Morse SJ; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Canales CP; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Stradleigh TW; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Castillo Palacios E; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Haghani V; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Moss SD; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Parolini H; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Quintero D; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Shrestha D; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States., Vogt D; Department of Pediatrics and Human Development, Grand Rapids Research Center, Michigan State University, Grand Rapids, United States., Byrne LC; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States.; Departments of Ophthalmology and Neurobiology, University of Pittsburgh, Pittsburgh, United States., Nord AS; Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States.; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Oct 04; Vol. 10. Date of Electronic Publication: 2021 Oct 04.
DOI:	10.7554/eLife.69479
Abstrakt:	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. Competing Interests: JL, LS, KC, TW, IZ, YW, KL, JH, SM, CC, TS, EC, VH, SM, HP, DQ, DS, DV, LB, AN No competing interests declared (© 2021, Lambert et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu