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Series GSE100384 Query DataSets for GSE100384
Status Public on Jan 17, 2018
Title Ultraconserved Enhancers Are Required for Normal Development [Drop-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Non-coding ultraconserved regions showing hundreds of consecutive bases of perfect evolutionary sequence conservation across mammalian genomes have intrigued biologists in the decade since they were first described. While many of these sequences are known to represent distant-acting enhancers, initial deletion studies in mice showed that their loss had no obvious impact on viability or fertility. To explore the discrepancy between extraordinary evolutionary constraint and an apparent lack of phenotypes when deleted in vivo, we used genome editing to create an expanded series of knockout mice lacking individual or combinations of ultraconserved brain enhancers near the essential neuronal transcription factor Arx. While the loss of any single or pair of ultraconserved enhancers resulted in viable and fertile mice, detailed phenotyping revealed neurological or growth abnormalities in nearly all cases, including substantial alterations of neuron populations and abnormalities of the dentate gyrus. Our results demonstrate the functional importance of ultraconserved enhancers and highlight that extreme sequence conservation may result from evolutionary selection against fitness deficits that appear subtle in a laboratory setting.
Overall design Cell suspensions were prepared from E12.5 mouse forebrains, and single-cell mRNAseq libraries were generated with Drop-Seq. Experiments were performed on transgenics embryos in which a validated forebrain enhancer (hs119, hs121, hs122, hs123, controlled the expression of a reporter gene (either GFP or mCherry).
Contributor(s) Dickel DE, Ypsilanti AR, Pla R, Zhu Y, Barozzi I, Mannion BJ, Khin Y, Fukuda-Yuzawa Y, Plajzer-Frick I, Pickle CS, Lee EE, Harrington AN, Pham QT, Garvin TH, Kato M, Akiyama JA, Afzal V, Rubenstein JL, Visel A, Pennacchio LA
Citation(s) 29358049
Submission date Jun 22, 2017
Last update date May 15, 2019
Contact name Iros Barozzi
Organization name Medical University Vienna
Street address Borschkegasse 8a
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL22245 Illumina HiSeq 2500 (Homo sapiens; Mus musculus)
Samples (6)
GSM2679965 hs119-GFP
GSM2679966 hs121-mCherry
GSM2679967 hs123-mCherry
This SubSeries is part of SuperSeries:
GSE100394 Ultraconserved Enhancers Are Required for Normal Development
BioProject PRJNA391516
SRA SRP110203

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Supplementary file Size Download File type/resource
GSE100384_dropseq_data.digital_expression.bulk.txt.gz 70.9 Kb (ftp)(http) TXT
GSE100384_dropseq_data.digital_expression.txt.gz 7.4 Mb (ftp)(http) TXT
GSE100384_mm10_hg19.refFlat.txt.gz 5.0 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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