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Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [ChIP-seq]

ABSTRACT: Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [ChIP-seq]

PROVIDER: PRJNA596780 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10740570.fastq.gz	Fastqsanger.gz
	SRR10740571.fastq.gz	Fastqsanger.gz
	SRR10740572.fastq.gz	Fastqsanger.gz
	SRR10740573.fastq.gz	Fastqsanger.gz
	SRR10740574.fastq.gz	Fastqsanger.gz

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Project description:While Hox genes encode for similar transcription factors (TFs), they induce different fates across body axes. We sought to understand how Hox TF genomic binding preferences relate to their patterning activities during neuronal differentiation. To generate the required neuronal diversity for locomotor activity, Hox TFs specify spinal motor neuron and interneuron subtypes along the rostro-caudal axis. Our data revelated that Hoxc6 and Hoxc8 of the central group induce limb-innervating fates by binding to the same sites. On the other hand, the posterior group Hox genes assign different positional identities: Hoxc9 (thoracic), Hoxc10 (limb-innervating) and Hox13 (axial elongation termination) by binding to distinct sites with the same primary motif. We find that their genomic binding distributions are explained by differential abilities to bind to previously inaccessible chromatin. Thus, the vertebrate posterior Hox expansion and its associated patterning diversification is the product of their differential abilities to associate with less accessible chromatin.

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Project description:Although 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.

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