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Tumour suppressors

Unfold with BRCA1

Nature Reviews Cancer volume 2, page 8 (2002)Cite this article

To investigate the effect of BRCA1 on chromatin structure, the authors used a cell line containing many copies of the lac operator, which forms a large heterochromatic region. Immunofluoresence using antibodies against the lac repressor — which binds to the lac operator sequences — allows the region to be visualized as a compact nuclear dot. Expression of a BRCA1–lac repressor fusion protein alters this structure in 14% of cells: it becomes irregularly shaped, indicative of chromatin unfolding. The authors used deletion analysis to identify three regions of BRCA1 that could induce this unfolding in BRCA1's carboxy-terminal transcriptional activation domain. They include activation domain 1 (AD1), and the two BRCA1 C terminus repeats (BRCT1 and BRCT2), which lie within AD2.

Histone modification is a known chromatin-regulation mechanism, so is this involved in BRCA1-mediated regulation? Unlike p53 and E2F1 — two other transcription factors that induce chromatin unfolding — BRCA1 does not induce hyperacetylation of histones H3 and H4. It does, however, induce phosphorylation of H2AX, a variant of histone H2A, although this has not been directly linked to chromatin regulation.

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ORIGINAL RESEARCH PAPERS

  1. Ye, Q. et al. BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations. J. Cell Biol. 155, 911–921 (2001)

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  1. Emma Greenwood
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Greenwood, E. Unfold with BRCA1. Nat Rev Cancer 2, 8 (2002). https://doi.org/10.1038/nrc714

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