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| Status |
Public on May 01, 2024 |
| Title |
Regulatory Functional Landscape of the HMX1 Gene for Normal Ear Development [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Enhancers, through the combinatorial action of transcription factors (TFs), dictate both the spatial specificity and the levels of gene expression, and their aberrations can result in diseases. The association between HMX1 and its downstream enhancer with ear deformities has been previously documented. However, the pathogenic variations and molecular mechanisms underlying the bilateral constricted ear (BCE) malformations remain unclear. This study identifies a copy number variation (CNV) encompassing three enhancers that induces BCE. These enhancers, collectively termed the positional identity hierarchical enhancer cluster (PI-HEC), co-regulate HMX1, each displaying unique activity-location-structure characteristics. A thorough exploration of this regulatory locus reveals that specific motif clusters within the PI-HEC variably modulate its activity and specificity, with the high mobility group (HMG) box combined with Coordinator and homeodomain (HD)-TFs notably influencing them respectively. Our findings based on various types of mouse models, reveal that both aberrant Hmx1 expression in the fibroblasts of the basal pinna, originating from neural crest cells, and ectopic expression in the distal pinna structures contribute to the abnormal development of the outer ear, including the cartilage, muscle, and epidermis tissues. This study deepens our understanding of mammalian ear morphogenesis and sheds light on the complexity of gene expression regulation by enhancers and specific sequence motifs.
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| Overall design |
Expression profiles of mouse embryo E14.5 pinna structure between wild-type and transgenic mEC1 knock-in (KI) mouse model
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| Contributor(s) |
Xu X, Zhang Y |
| Citation missing |
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| Submission date |
Apr 02, 2024 |
| Last update date |
May 01, 2024 |
| Contact name |
Xu Xiaopeng |
| E-mail(s) |
xu_xiaopeng@gzlab.ac.cn
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| Organization name |
Guangzhou National Laboratory
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| Street address |
96 Xingdao South Road, Guangzhou International Bio Island, Haizhu District
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| City |
Guangzhou |
| ZIP/Postal code |
510320 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA1095583 |
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