Abstract
Aebp2 is a potential targeting protein for the mammalian Polycomb Repression Complex 2 (PRC2). We generated a mutant mouse line disrupting the transcription of Aebp2 to investigate its in vivo roles. Aebp2-mutant homozygotes were embryonic lethal while heterozygotes survived to adulthood with fertility. In developing mouse embryos, Aebp2 is expressed mainly within cells of neural crest origin. In addition, many heterozygotes display a set of phenotypes, enlarged colon and hypopigmentation, similar to those observed in human patients with Hirschsprung's disease and Waardenburg syndrome. These phenotypes are usually caused by the absence of the neural crest-derived ganglia in hindguts and melanocytes. ChIP analyses demonstrated that the majority of the genes involved in the migration and development process of neural crest cells are downstream target genes of AEBP2 and PRC2. Furthermore, expression analyses confirmed that some of these genes are indeed affected in the Aebp2 heterozygotes. Taken together, these results suggest that Aebp2 may regulate the migration and development of the neural crest cells through the PRC2-mediated epigenetic mechanism.
Highlights
Adipocyte Enhancer Binding Protein 2 (Aebp2) is an evolutionarily well conserved Gli-type zinc finger gene that is found in species ranging from flying insects to humans [1]
We identified the 59- and 39-side junction regions between the by the gene trap vector (b-Geo) vector and the surrounding genomic regions, which subsequently allowed us to develop a set of three primers that could be used for genotyping the embryos derived from the breeding of this mutant line (Fig. 1B)
The half dosage of Aebp2 appears to be insufficient for the proper development of some neural crest cells that the Aebp2 heterozygotes (Aebp2+/b-Geo or b-Geo/+) display a set of phenotypes very similar to those from Hirschsprung’s disease (HSCR) and Waardenburg syndrome (WS)
Summary
Aebp is an evolutionarily well conserved Gli-type zinc finger gene that is found in species ranging from flying insects to humans [1]. This gene was initially identified due to its binding capability to the promoter of the adipocyte P2 gene, named Adipocyte Enhancer Binding Protein 2 (Aebp2) [2]. Long non-coding RNAs are shown to be involved in recruiting PRC2 to a subset of genomic loci. Many of these target genes turn out to be cancerrelated genes [8]. These studies suggest the presence of many independent targeting mechanisms for PRC2, consistent with the fact that PRC2 likely plays diverse roles in various cell types and tissues [9,10]
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