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Ronin Governs Early Heart Development by Controlling Core Gene Expression Programs.

ABSTRACT: Ronin (THAP11), a DNA-binding protein that evolved from a primordial DNA transposon by molecular domestication, recognizes a hyperconserved promoter sequence to control developmentally and metabolically essential genes in pluripotent stem cells. However, it remains unclear whether Ronin or related THAP proteins perform similar functions in development. Here, we present evidence that Ronin functions within the nascent heart as it arises from the mesoderm and forms a four-chambered organ. We show that Ronin is vital for cardiogenesis during midgestation by controlling a set of critical genes. The activity of Ronin coincided with the recruitment of its cofactor, Hcf-1, and the elevation of H3K4me3 levels at specific target genes, suggesting the involvement of an epigenetic mechanism. On the strength of these findings, we propose that Ronin activity during cardiogenesis offers a template to understand how important gene programs are sustained across different cell types within a developing organ such as the heart.

SUBMITTER: Fujita J

PROVIDER: S-EPMC5695914 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Ronin governs early heart development by controlling core gene programs

Project description:Ronin (THAP11), an idiosyncratic DNA-binding protein that evolved from a primordial DNA transposon by molecular domestication, recognizes a hyperconserved promoter sequence through which it controls a variety of developmentally and metabolically essential genes in pluripotent stem cells. However, it remains unclear whether Ronin or related THAP proteins perform similar functions elsewhere in development. Here, we present evidence indicating that Ronin performs a novel function within the nascent heart as it arises from the mesoderm and forms a four-chambered organ. We show that Ronin is vital for cardiogenesis during midgestation through its control of a core set of critical genes. The activity of Ronin coincided with the recruitment of its cofactor, Hcf-1, and the elevation of H3K4me3 levels at specific target genes, suggesting the involvement of an epigenetic mechanism. On the strength of these findings, we propose that Ronin activity during cardiogenesis may offer a template that could be used to understand how important gene programs are sustained across different cell types within a developing organ, such as the heart.

2017-09-19 | GSE103959 | GEO

Ronin governs early heart development by controlling core gene programs

Project description:Ronin governs early heart development by controlling core gene programs

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Ronin governs the metabolic capacity of the embryonic lineage for post-implantation development.

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Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function.

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