Ronin Governs Early Heart Development by Controlling Core Gene Expression Programs

Cell Rep. 2017 Nov 7;21(6):1562-1573. doi: 10.1016/j.celrep.2017.10.036.


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.

Keywords: dilative cardiomyopathy; heart development; heart disease; organ growth; transcriptional control.

MeSH terms

  • Animals
  • Bradycardia / metabolism
  • Bradycardia / physiopathology
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / physiopathology
  • Chromatin Immunoprecipitation
  • Echocardiography
  • Embryo, Mammalian / metabolism
  • Embryonic Development
  • Gene Expression Regulation, Developmental
  • Heart / diagnostic imaging
  • Heart / growth & development*
  • Histones / genetics
  • Histones / metabolism
  • Homeobox Protein Nkx-2.5 / deficiency
  • Homeobox Protein Nkx-2.5 / genetics
  • Host Cell Factor C1 / genetics
  • Host Cell Factor C1 / metabolism
  • Methylation
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Myosin Heavy Chains / deficiency
  • Myosin Heavy Chains / genetics
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Initiation Site


  • Hcfc1 protein, mouse
  • Histones
  • Homeobox Protein Nkx-2.5
  • Host Cell Factor C1
  • Myh6 protein, mouse
  • Nkx2-5 protein, mouse
  • Repressor Proteins
  • Thap11 protein, mouse
  • Myosin Heavy Chains