{
  "abstract": "BACH1 is a heme-regulated basic-leucine-zipper containing transcriptional repressor that binds its DNA recognition elements as a heterodimer with MAFK. Heme-binding is thought to be mediated by several Cys-Proline (CP) motifs and this results in dissociation of the heterodimer from DNA. The mechanism of heme-binding and heme-mediated DNA dissociation remains unresolved. We have used UV-visible spectroscopy, 2D-NMR and DNA-binding assays to explore both heme-binding and DNA dissociation of a minimal BACH1 construct containing 2 CP motifs (C492(CP5) and C646(CP6)) flanking the DNA-binding domain. We find that heme is able to bind to both CP motifs, but also to other non-CP cysteines and histidines in the construct. Using NMR spectroscopy, we identify a structured binding pocket in which heme interacts with both C646(CP6) and Cys621. However, DNA-binding assays show that C646(CP6) is not required for heme-mediated DNA dissociation of the BACH1:MAFK heterodimer. Using UV-visible spectroscopy we show that C492(CP5) also recruits heme with a second ligand, a conserved histidine, His559, in the BACH1 DNA-recognition helix. Mutation of C492(CP5) reduces but does not abolish heme-mediated dissociation from DNA. Our findings suggest a mechanism for heme-binding to BACH1 and heme-mediated dissociation from DNA.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Structural and Chemical Biology, Division of Molecular and Cell Biology, University of Leicester"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Y. Huang"
    },
    {
      "name": "L. Fairall"
    },
    {
      "name": "F. W. Muskett"
    },
    {
      "name": "C. Dominguez"
    },
    {
      "name": "A. Hudson"
    },
    {
      "affs": [
        0
      ],
      "name": "J. W. Schwabe"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a1bvc91eq3wq8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.28.747782",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747782v1.full",
  "id": "a1bvc91eq3wq8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747782v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "1307|Hemoglobin structure and function"
    ]
  ],
  "openalex": "W7204776970",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747782v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a1bvc91eq3wq8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.64898/2026.08.28.747782",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747782v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Hemoglobin structure and function",
      "subfield": "cell-biology"
    }
  ],
  "title": "Mechanism of heme binding by CP motifs in the BACH1 DNA-binding region",
  "title_text": "Mechanism of heme binding by CP motifs in the BACH1 DNA-binding region",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/a1bvc91eq3wq8",
  "venue": "bioRxiv",
  "versions": []
}