Autoren:	Chan, Ya-Chien Kienle, Eike Oti, Martin Di Liddo, Antonella Mendez-Lago, Maria Aschauer, Dominik F. Peter, Manuel Pagani, Michaela Arnold, Cosmas Vonderheit, Andreas Schön, Christian Kreuz, Sebastian Stark, Alexander Rumpel, Simon
Titel:	An unbiased AAV-STARR-seq screen revealing the enhancer activity map of genomic regions in the mouse brain in vivo
Online-Publikationsdatum:	24-Jan-2024
Erscheinungsdatum:	2023
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Enhancers are important cis-regulatory elements controlling cell-type specific expression patterns of genes. Furthermore, combinations of enhancers and minimal promoters are utilized to construct small, artificial promoters for gene delivery vectors. Large-scale functional screening methodology to construct genomic maps of enhancer activities has been successfully established in cultured cell lines, however, not yet applied to terminally differentiated cells and tissues in a living animal. Here, we transposed the Self-Transcribing Active Regulatory Region Sequencing (STARR-seq) technique to the mouse brain using adeno-associated-viruses (AAV) for the delivery of a highly complex screening library tiling entire genomic regions and covering in total 3 Mb of the mouse genome. We identified 483 sequences with enhancer activity, including sequences that were not predicted by DNA accessibility or histone marks. Characterizing the expression patterns of fluorescent reporters controlled by nine candidate sequences, we observed differential expression patterns also in sparse cell types. Together, our study provides an entry point for the unbiased study of enhancer activities in organisms during health and disease.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9966
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart:	Scientific article
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Scientific reports 13
Seitenzahl oder Artikelnummer:	6745
Verlag:	Macmillan Publishers Limited, part of Springer Nature
Verlagsort:	London
Erscheinungsdatum:	2023
ISSN:	2045-2322
DOI der Originalveröffentlichung:	10.1038/s41598-023-33448-w
Enthalten in den Sammlungen:	DFG-491381577-G