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Title: Foxp transcription factors suppress a non-pulmonary gene expression program to permit proper lung development.

Authors: Li, Shanru; Morley, Michael; Lu, MinMin; Zhou, Su; Stewart, Kathleen; French, Catherine A; Tucker, Haley O; Fisher, Simon E; Morrisey, Edward E

Published In Dev Biol, (2016 08 15)

Abstract: The inhibitory mechanisms that prevent gene expression programs from one tissue to be expressed in another are poorly understood. Foxp1/2/4 are forkhead transcription factors that repress gene expression and are individually important for endoderm development. We show that combined loss of all three Foxp1/2/4 family members in the developing anterior foregut endoderm leads to a loss of lung endoderm lineage commitment and subsequent development. Foxp1/2/4 deficient lungs express high levels of transcriptional regulators not normally expressed in the developing lung, including Pax2, Pax8, Pax9 and the Hoxa9-13 cluster. Ectopic expression of these transcriptional regulators is accompanied by decreased expression of lung restricted transcription factors including Nkx2-1, Sox2, and Sox9. Foxp1 binds to conserved forkhead DNA binding sites within the Hoxa9-13 cluster, indicating a direct repression mechanism. Thus, Foxp1/2/4 are essential for promoting lung endoderm development by repressing expression of non-pulmonary transcription factors.

PubMed ID: 27341756 Exiting the NIEHS site

MeSH Terms: Animals; Binding Sites; Conserved Sequence; DNA/genetics; DNA/metabolism; Endoderm/cytology; Endoderm/embryology; Forkhead Transcription Factors/deficiency; Forkhead Transcription Factors/genetics*; Forkhead Transcription Factors/metabolism; Gene Expression Regulation, Developmental*; Genes, Homeobox; Lung/embryology*; Mice; Organ Specificity; Organogenesis; Repressor Proteins/deficiency; Repressor Proteins/genetics*; Repressor Proteins/metabolism; Sequence Alignment; Sequence Homology, Nucleic Acid; Transcription Factors/biosynthesis; Transcription Factors/genetics

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