HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation
Baker, Syed Murtuza
Sagerstrom, Charles G.
Mace, Kimberly A.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
KeywordsSequence motif analysis
Biochemistry, Biophysics, and Structural Biology
Cell and Developmental Biology
Genetics and Genomics
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AbstractGene 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.
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