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.

蛋白质通过建立，维持和解构特定于细胞类型的染色体景观来控制基因组功能。大量的小分子协调细胞功能，因此可能将生理过程与基因组生物学联系起来。代谢酶和血红蛋白辅因子血红素诱导转录阻遏物Bach1的蛋白水解，并在转录后调节基因表达。然而，尚不清楚血红素是广泛控制基因组功能还是通过规定作用来控制基因组功能。使用转座酶可及的染色质测序（ATAC-seq）的测定，我们在缺乏赋予正常血红素合成功能的增强子的野生型和突变型成红细胞中建立了血红素依赖性染色质图谱。具有亚生理血红素和血红素后拯救的细胞中的染色质景观和转录组融合，揭示了针对血红素敏感染色体热点的平行Bach1依赖性和Bach1依赖性机制。热点区域带有一个DNA图案，该图案划分了血红素调节的染色质和编码未知的血红素调节蛋白（包括代谢酶）的基因。血液组学分析确定了必需的生化辅助因子如何控制基因组功能和细胞生理。