Heritable, allele-specific chromosomal looping between tandem promoters specifies promoter usage of SHC1

Xichuan Li, Zhenzhen Lin, Hao Wang, Dan Zhao, Xing Xu, Yiliang Wei, Xiaoting Li, Xiaobo Li, Yougui Xiang, Lance S. Terada, Zhe Liu

Research output: Contribution to journalArticle

Abstract

One-half of the genes in the human genome contain alternative promoters, some of which generate products with opposing functions. Aberrant silencing or activation of such alternative promoters is associated with multiple diseases, including cancer, but little is known regarding the molecular mechanisms that control alternative promoter choice. The SHC1 gene encodes p46 Shc /p52 Shc and p66 Shc , proteins oppositely regulating anchorage-independent growth that are produced by transcription initiated from the upstream and downstream tandem promoters of SHC1, respectively. Here we demonstrate that activation of these promoters is mutually exclusive on separate alleles in single primary endothelial cells in a heritable fashion, ensuring expression of both transcripts by the cell. Peripheral blood lymphocytes that do not transcribe p66 Shc transcribed p52 Shc biallelically. This distinct monoallelic transcription pattern is established by allele-specific chromosomal looping between tandem promoters, which silences the upstream promoter. Our results reveal a new mechanism to control alternative promoter usage through higher-order chromatin structure.

Original languageEnglish (US)
Article numbere00658-17
JournalMolecular and cellular biology
Volume38
Issue number9
DOIs
StatePublished - May 1 2018

Keywords

  • Allele-specific transcription
  • Alternative promoter interaction
  • Gene silencing
  • SHC1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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