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doi: 10.1242/10.1242/dev.00471

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Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression

Tim Brend^1,2, Jonathan Gilthorpe^2,*, Dennis Summerbell^1,2 and Peter W. J. Rigby^1,2,

¹ Section of Gene Function and Regulation, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
² Division of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
^* Present address: Department of Developmental Neurobiology, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK

Author for correspondence (e-mail: Peter.Rigby{at}icr.ac.uk)

Accepted 5 March 2003

Hox genes are key determinants of anteroposterior patterning of animal embryos, and spatially restricted expression of these genes is crucial to this function. In this study, we demonstrate that expression of Hoxb4 in the paraxial mesoderm of the mouse embryo is transcriptionally regulated in several distinct phases, and that multiple regulatory elements interact to maintain the complete expression domain throughout embryonic development. An enhancer located within the intron of the gene (region C) is sufficient for appropriate temporal activation of expression and the establishment of the correct anterior boundary in the paraxial mesoderm (somite 6/7). However, the Hoxb4 promoter is required to maintain this expression beyond 8.5 dpc. In addition, sequences within the 3' untranslated region (region B) are necessary specifically to maintain expression in somite 7 from 9.0 dpc onwards. Neither the promoter nor region B can direct somitic expression independently, indicating that the interaction of regulatory elements is crucial for the maintenance of the paraxial mesoderm domain of Hoxb4 expression. We further report that the domain of Hoxb4 expression is restricted by regulating transcript stability in the paraxial mesoderm and by selective translation and/or degradation of protein in the neural tube. Moreover, the absence of Hoxb4 3'-untranslated sequences from transgene transcripts leads to inappropriate expression of some Hoxb4 transgenes in posterior somites, indicating that there are sequences within region B that are important for both transcriptional and post-transcriptional regulation.

Key words: Hoxb4, Paraxial mesoderm, Anterior boundary, Maintenance, Transcription, RNA stability, Translation, Mouse

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