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Enhancer DNA pull-down of proteins extracted from PA2 tissue of mouse E11.5 embryos

ABSTRACT: 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. While HMX1 downstream enhancer is associated to ear malformations, the mechanisms underlying bilateral constricted ear (BCE) remain unclear. Here, we identify a copy number variation (CNV) containing three enhancers—collectively termed the positional identity hierarchical enhancer cluster (PI-HEC)—that drives BCE by coordinately regulating HMX1 expression. Each enhancer exhibits distinct activity-location-structure features, and the dominant enhancer with high mobility group (HMG)-box and homeodomain TF motifs modulating its activity and specificity, respectively. Mouse models demonstrate that neural crest-derived fibroblasts with aberrant Hmx1 expression in the basal pinna, along with ectopic distal pinna expression, disrupt outer ear development, affecting cartilage, muscle, and epidermis. Our findings elucidate mammalian ear morphogenesis and underscore the complexity of synergistic regulation among enhancers and between enhancers and transcription factors.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryo

SUBMITTER: Xiaopeng Xu

LAB HEAD: Yong-Biao Zhang

PROVIDER: PXD063373 | Pride | 2025-04-28

REPOSITORIES: Pride

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			Action	DRS
	F001505.csv	Csv
	F001505.xlsx	Xlsx
	F001506.csv	Csv
	F001506.xlsx	Xlsx
	ZTT-NC.mgf	Mgf

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