Department of Biochemistry and Molecular Pharmacology
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics
Gene expression programs determine cell fate in embryonic development and their dysregulation results in disease. Transcription factors (TFs) control gene expression by binding to enhancers, but how TFs select and activate their target enhancers is still unclear. HOX TFs share conserved homeodomains with highly similar sequence recognition properties, yet they impart the identity of different animal body parts. To understand how HOX TFs control their specific transcriptional programs in vivo, we compared HOXA2 and HOXA3 binding profiles in the mouse embryo. HOXA2 and HOXA3 directly cooperate with TALE TFs and selectively target different subsets of a broad TALE chromatin platform. Binding of HOX and tissue-specific TFs convert low affinity TALE binding into high confidence, tissue-specific binding events, which bear the mark of active enhancers. We propose that HOX paralogs, alone and in combination with tissue-specific TFs, generate tissue-specific transcriptional outputs by modulating the activity of TALE TFs at selected enhancers.
Sequence motif analysis, Gene expression, Chromatin, Homeobox, Mammalian genomics, Acetylation, DNA transcription, Transfection
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Copyright: © 2020 Bridoux et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Bridoux L, Zarrineh P, Mallen J, Phuycharoen M, Latorre V, Ladam F, Losa M, Baker SM, Sagerstrom C, Mace KA, Rattray M, Bobola N. HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation. PLoS Genet. 2020 Dec 14;16(12):e1009162. doi: 10.1371/journal.pgen.1009162. PMID: 33315856; PMCID: PMC7769617. Link to article on publisher's site
Bridoux L, Zarrineh P, Mallen J, Phuycharoen M, Latorre V, Ladam F, Losa M, Baker SM, Sagerstrom CG, Mace KA, Rattray M, Bobola N. (2020). HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation. Open Access Publications by UMMS Authors. https://doi.org/10.1371/journal.pgen.1009162. Retrieved from https://escholarship.umassmed.edu/oapubs/4517
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