Genomics

Dataset Information

93

The transcription factor Isl1 is associated with multiple signalling pathways important during genital development


ABSTRACT: To identify regulatory targets of the transcription factor Isl1 in the developing mouse genitalia, we performed ChIP-Seq using an anti-ISL1 rabbit monoclonal antibody on pooled chromatin isolated from multiple E14.5 mouse embryonic genital tubercles (GT). Our analysis identified more than 7,054 genomic regions enriched in both of two replicates. The majority of these binding sites are located more than 5 kb from the closest annotated transcriptional start site (TSS), with nearly one third of the binding sites more than 50kb away from the nearest TSS. A de novo motif search using HOMER demonstrated that GT Isl1 ChIP-seq peaks are enriched for a motif that matches the consensus sequence bound by Isl1 in other tissues. When compared to active enhancers in the GT identified using H3K27ac ChIP-Seq, we found that Isl1 binding sites are strongly enriched in the GT compared to other embryonic tissues. Further analysis of the location of Isl1 peaks revealed a strong association with genes implicated in limb and urogenital development. We conclude that there is a strong association between Isl1 regulatory activity and genes involved in genital development. Overall design: Examination of Isl1 transcription factor binding in two replicates of chromatin isolated from the developing genital tubercles of E14.5 mouse embryos using ChIP-Seq.

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

SUBMITTER: Carlos Rafael Infante  

PROVIDER: GSE91082 | GEO | 2017-11-08

SECONDARY ACCESSION(S): PRJNA356836

REPOSITORIES: GEO

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Publications

Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a.

Ching Saunders T ST   Infante Carlos R CR   Du Wen W   Sharir Amnon A   Park Sungdae S   Menke Douglas B DB   Klein Ophir D OD  

Human molecular genetics 20180101 1


Genital malformations are among the most common human birth defects, and both genetic and environmental factors can contribute to these malformations. Development of the external genitalia in mammals relies on complex signaling networks, and disruption of these signaling pathways can lead to genital defects. Islet-1 (ISL1), a member of the LIM/Homeobox family of transcription factors, has been identified as a major susceptibility gene for classic bladder exstrophy in humans, a common form of the  ...[more]

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