title: A regulatory domain is required for Foxn4 activity during retinogenesis.
abstract: Foxn4, a member of the N-family forkhead transcription factors, controls fate decision in mouse retina and spinal cord as well as in zebrafish heart. Analysis of Foxn4 amino acid sequence revealed the presence of a region homologous to the activation domain of its close relative Foxn1 in between C-terminal amino acids 402 and 455 of Foxn4 protein. The requirement of Foxn4 putative activation domain remains to be elucidated. Using a gain-of function approach in rat and chick retinal explants, we report that deletion of Foxn4 putative activation domain results in a complete loss of its activity during retinogenesis. Target promoter transcription assay indicates that this domain is critical for Foxn4 transcriptional regulatory properties in vitro. Accordingly, in chick retinal explants, this domain is required for proper regulation of target retinogenic factors expression by Foxn4. Thus, our study demonstrates that the domain between amino acids 402 and 455 is necessary for Foxn4 transcriptional activity both in vitro and in the retina.
authors.affiliation: Centre de Recherche des Cordeliers, INSERM UMR S872, 15, Rue de L'Ecole de Médecine, 75006, Paris, France.
authors.forename: Elise C
authors.initials: EC
authors.lastname: Lelièvre
authors.forename: Bérénice A
authors.initials: BA
authors.lastname: Benayoun
authors.forename: Laurence
authors.initials: L
authors.lastname: Mahieu
authors.forename: Jérome E
authors.initials: JE
authors.lastname: Roger
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
authors.forename: Olivier
authors.initials: O
authors.lastname: Goureau
authors.forename: Xavier
authors.initials: X
authors.lastname: Guillonneau
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D009924:Organ Culture Techniques; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012160:Retina / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D005136:Eye Proteins; D051858:Forkhead Transcription Factors; C438622:Foxn4 protein, mouse; C574893:Foxn4 protein, rat; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C090140:Whn protein