Identification of a face enhancer reveals direct regulation of LIM homeobox 8 (Lhx8) by wingless-int (WNT)/β-catenin signaling

André Landin Malt, Jeffry M. Cesario, Zuojian Tang, Stuart Brown, Juhee Jeong

Research output: Contribution to journalArticle

Abstract

Development of the mammalian face requires a large number of genes that are expressed with spatio-temporal specificity, and transcriptional regulation mediated by enhancers plays a key role in the precise control of gene expression. Using chromatin immunoprecipitation for a histone marker of active enhancers, we generated a genome-wide map of candidate enhancers from the maxillary arch (primordium for the upper jaw) of mouse embryos. Furthermore, we confirmed multiple novel craniofacial enhancers near the genes implicated in human palate defects through functional assays. We characterized in detail one of the enhancers (Lhx8-enh1) located upstream of Lhx8, a key regulatory gene for craniofacial development. Lhx8-enh1 contained an evolutionarily conserved binding site for lymphoid enhancer factor/T-cell factor family proteins, which mediate the transcriptional regulation by the WNT/β-catenin signaling pathway.Wedemonstrated in vitro that WNT/β-catenin signaling was indeed essential for the expression of Lhx8 in the maxillary arch cells and that Lhx8-enh1 was a direct target of the WNT/β-catenin pathway. Together, we uncovered a molecular mechanism for the regulation of Lhx8, and we provided valuable resources for further investigation into the gene regulatory network of craniofacial development.

Original languageEnglish (US)
Pages (from-to)30289-30301
Number of pages13
JournalJournal of Biological Chemistry
Volume289
Issue number44
DOIs
StatePublished - Oct 31 2014

Fingerprint

Catenins
Homeobox Genes
Genes
TCF Transcription Factors
Arches
Gene expression
Palate
Gene Regulatory Networks
Chromatin Immunoprecipitation
Histones
Maxilla
Chromatin
Regulator Genes
Assays
Binding Sites
Embryonic Structures
Defects
Genome
Gene Expression
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Identification of a face enhancer reveals direct regulation of LIM homeobox 8 (Lhx8) by wingless-int (WNT)/β-catenin signaling. / Malt, André Landin; Cesario, Jeffry M.; Tang, Zuojian; Brown, Stuart; Jeong, Juhee.

In: Journal of Biological Chemistry, Vol. 289, No. 44, 31.10.2014, p. 30289-30301.

Research output: Contribution to journalArticle

Malt, André Landin ; Cesario, Jeffry M. ; Tang, Zuojian ; Brown, Stuart ; Jeong, Juhee. / Identification of a face enhancer reveals direct regulation of LIM homeobox 8 (Lhx8) by wingless-int (WNT)/β-catenin signaling. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 44. pp. 30289-30301.
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