HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

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...

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Bibliographic Details
Published in:PLoS genetics 2020-12, Vol.16 (12), p.e1009162-e1009162
Main Authors: Bridoux, Laure, Zarrineh, Peyman, Mallen, Joshua, Phuycharoen, Mike, Latorre, Victor, Ladam, Frank, Losa, Marta, Baker, Syed Murtuza, Sagerstrom, Charles, Mace, Kimberly A, Rattray, Magnus, Bobola, Nicoletta
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Analysis
Animals
Binding sites
Biology and Life Sciences
Cell fate
Comparative analysis
Deoxyribonucleic acid
DNA
Embryogenesis
Enhancer Elements, Genetic
Gene expression
Gene Expression Regulation, Developmental
Genomes
Homeodomain Proteins - chemistry
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Homeostasis
Hox genes
Mice
Nucleotide sequence
Organ Specificity
Phase transitions
Physical Sciences
Physiological aspects
Physiology
Protein Binding
Proteins
Regulatory proteins
Research and Analysis Methods
Transcription factors
Transcription Factors - metabolism
Transcriptional Activation
Transcriptional coactivators
Zebrafish
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1009162