Research resource: A genome-wide study identifies potential new target genes for POU1F1.
The pituitary transcription factor POU1F1 is required for the differentiation of lactotrope, thyrotrope, and somatotrope cells. Its expression is maintained in the adult and is crucial for the expression of prolactin, GH, and TSHβ-subunit. Different studies indicated that POU1F1 could also have other functions in these cells. The identification of new targets of this factor could be useful to obtain a better understanding of these functions. To address this question we combined data obtained from expression microarrays and from chromatin immunoprecipitation (ChIP)-chips. Gene expression microarray assays were used to detect genes that have their expression modified in somatolactotrope GH4C1 cells by the expression of a dominant-negative form of POU1F1, POU1F1(R271W), and led to the identification of 1346 such genes. ChIP-chip experiments were performed from mouse pituitaries and identified 1671 POU1F1-binding sites in gene-promoter regions. Intersecting the gene expression and the ChIP-chip data yielded 121 potential new direct targets. The initial set of 1346 genes identified using the microarrays, as well as the 121 potential new direct targets, were analyzed with DAVID bioinformatics resource for gene ontology term enrichment and cluster. This analysis revealed enrichment in different terms related to protein synthesis and transport, to apoptosis, and to cell division. The present study represents an integrative genome-wide approach to identify new target genes of POU1F1 and downstream networks controlled by this factor.
Centre National de la Recherche Scientifique, CRN2M-Unité Mixte de Recherche 7286, F-13344 Marseille, France.
Jean-Paul
JP
Herman
Nicolas
N
Jullien
Séverine
S
Guillen
Alain
A
Enjalbert
Isabelle
I
Pellegrini
Jean-Louis
JL
Franc
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D047369:Chromatin Immunoprecipitation; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005799:Genes, Dominant; D015894:Genome, Human; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050817:Transcription Factor Pit-1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome
D048868:Adaptor Proteins, Signal Transducing; C497410:CREM protein, human; D060588:LIM Domain Proteins; C114905:LMO4 protein, human; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D051786:Cyclic AMP Response Element Modulator