Epigenomic profiling of retinal progenitors reveals LHX2 is required for developmental regulation of open chromatin

Commun Biol. 2019 Apr 25;2:142. doi: 10.1038/s42003-019-0375-9. eCollection 2019.

Abstract

Retinal neurogenesis occurs through partially overlapping temporal windows, driven by concerted actions of transcription factors which, in turn, may contribute to the establishment of divergent genetic programs in the developing retina by coordinating variations in chromatin landscapes. Here we comprehensively profile murine retinal progenitors by integrating next generation sequencing methods and interrogate changes in chromatin accessibility at embryonic and post-natal stages. An unbiased search for motifs in open chromatin regions identifies putative factors involved in the developmental progression of the epigenome in retinal progenitor cells. Among these factors, the transcription factor LHX2 exhibits a developmentally regulated cis-regulatory repertoire and stage-dependent motif instances. Using loss-of-function assays, we determine LHX2 coordinates variations in chromatin accessibility, by competition for nucleosome occupancy and secondary regulation of candidate pioneer factors.

Keywords: Developmental neurogenesis; Epigenomics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin / metabolism
  • Chromatin Immunoprecipitation Sequencing
  • Epigenomics / methods*
  • Female
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Knockout Techniques
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Neurogenesis / genetics*
  • Nucleosomes / metabolism
  • RNA-Seq
  • Retina / embryology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Chromatin
  • LIM-Homeodomain Proteins
  • Lhx2 protein, mouse
  • Nucleosomes
  • Transcription Factors