Abstract
ABSTRACTAlthough Hox genes encode for conserved transcription factors (TFs), they are further divided into anterior, central and posterior groups based on their DNA-binding domain similarity. The posterior Hox group expanded in the deuterostome clade and patterns caudal and distal structures. We aimed to address how similar Hox TFs diverge to induce different positional identities. We studied Hox TF DNA-binding and regulatory activity during an in vitro motor neuron differentiation system that recapitulates embryonic development. We found diversity in the genomic binding profiles of different Hox TFs, even among the posterior group paralogs that share similar DNA-binding domains. These differences in genomic binding were explained by differing abilities to bind to previously inaccessible sites. For example, the posterior group HOXC9 had a greater ability to bind occluded sites than the posterior HOXC10, producing different binding patterns and driving differential gene expression programs. From these results, we propose that the differential abilities of posterior Hox TFs to bind to previously inaccessible chromatin drive patterning diversification.This article has an associated ‘The people behind the papers’ interview.
Highlights
Hox genes encode a highly conserved transcription factor (TF) family that endows cells with positional identity during embryonic development (McGinnis and Krumlauf, 1992; Lewis, 1978; Duboule and Dolle, 1989)
Surprisingly little is known about how vertebrate Hox TFs bind to the genome in a cellular-relevant environment
To gain insights into Hox activity, we performed a multilevel comparison of global binding patterns, chromatin accessibility preferences and transcriptional target genes of seven Hox proteins expressed under the same developmentally relevant conditions
Summary
Hox genes encode a highly conserved transcription factor (TF) family that endows cells with positional identity during embryonic development (McGinnis and Krumlauf, 1992; Lewis, 1978; Duboule and Dolle, 1989). Hox genes are organized into four clusters located on different chromosomes (HoxA, HoxB, HoxC and HoxD). Each cluster contains a subset of 13 similar paralogous Hox genes, genomically arranged in the same linear. Handling Editor: James Briscoe Received 6 July 2020; Accepted 25 September 2020 order as their spatial and temporal expression patterns in the developing embryo, a phenomenon known as collinearity (Kmita and Duboule, 2003; Duboule and Morata, 1994). Changes in Hox gene expression patterns induce gross morphological changes, resulting in well-characterized homeotic transformations. How Hox TFs assign different positional identities during cell differentiation is not entirely understood
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