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Discovering How Heme Controls Genome Function Through Heme-omics. Cell Rep 2020 Jun 30;31(13):107832

Date

07/02/2020

Pubmed ID

32610133

Pubmed Central ID

PMC7382780

DOI

10.1016/j.celrep.2020.107832

Scopus ID

2-s2.0-85086947598 (requires institutional sign-in at Scopus site)   16 Citations

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.

Author List

Liao R, Zheng Y, Liu X, Zhang Y, Seim G, Tanimura N, Wilson GM, Hematti P, Coon JJ, Fan J, Xu J, Keles S, Bresnick EH

Author

Peiman Hematti MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Basic-Leucine Zipper Transcription Factors
Cell Differentiation
Chromatin
Chromatin Assembly and Disassembly
Erythroid Cells
GATA1 Transcription Factor
Gene Expression Regulation
Gene Regulatory Networks
Genome
Heme
Humans
Male
Mice
Models, Biological
Nucleotide Motifs