Discovering How Heme Controls Genome Function Through Heme-omics

Ruiqi Liao, Ye Zheng, Xin Liu, Yuannyu Zhang, Gretchen Seim, Nobuyuki Tanimura, Gary M. Wilson, Peiman Hematti, Joshua J. Coon, Jing Fan, Jian Xu, Sunduz Keles, Emery H. Bresnick

Research output: Contribution to journalArticle

Abstract

Protein ensembles control genome function by establishing, maintaining, and deconstructing cell-type-specific chromosomal landscapes. A plethora of small molecules orchestrate cellular functions and therefore may link physiological processes with genome biology. The metabolic enzyme and hemoglobin cofactor heme induces proteolysis of a transcriptional repressor, Bach1, and regulates gene expression post-transcriptionally. However, whether heme controls genome function broadly or through prescriptive actions is unclear. Using assay for transposase-accessible chromatin sequencing (ATAC-seq), we establish a heme-dependent chromatin atlas in wild-type and mutant erythroblasts lacking enhancers that confer normal heme synthesis. Amalgamating chromatin landscapes and transcriptomes in cells with sub-physiological heme and post-heme rescue reveals parallel Bach1-dependent and Bach1-independent mechanisms that target heme-sensing chromosomal hotspots. The hotspots harbor a DNA motif demarcating heme-regulated chromatin and genes encoding proteins not known to be heme regulated, including metabolic enzymes. The heme-omics analysis establishes how an essential biochemical cofactor controls genome function and cellular physiology.

Original languageEnglish (US)
Article number107832
JournalCell Reports
Volume31
Issue number13
DOIs
StatePublished - Jun 30 2020

Keywords

  • ATAC-seq
  • Bach1
  • chromatin
  • erythroblast
  • erythroid
  • GATA1
  • heme
  • transcriptome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Liao, R., Zheng, Y., Liu, X., Zhang, Y., Seim, G., Tanimura, N., Wilson, G. M., Hematti, P., Coon, J. J., Fan, J., Xu, J., Keles, S., & Bresnick, E. H. (2020). Discovering How Heme Controls Genome Function Through Heme-omics. Cell Reports, 31(13), [107832]. https://doi.org/10.1016/j.celrep.2020.107832