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Short tandem repeats bind transcription factors to tune eukaryotic gene expression.

Publication ,  Journal Article
Horton, CA; Alexandari, AM; Hayes, MGB; Marklund, E; Schaepe, JM; Aditham, AK; Shah, N; Suzuki, PH; Shrikumar, A; Afek, A; Greenleaf, WJ ...
Published in: Science
September 22, 2023

Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density, with impacts well predicted by statistical mechanics. Confirming that STRs also affect TF binding in cells, neural networks trained only on in vivo occupancies predicted effects identical to those observed in vitro. Approximately 90% of TFs preferentially bound STRs that need not resemble known motifs, providing a cis-regulatory mechanism to target TFs to genomic sites.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

September 22, 2023

Volume

381

Issue

6664

Start / End Page

eadd1250

Location

United States

Related Subject Headings

  • Transcription Factors
  • Saccharomyces cerevisiae
  • Protein Domains
  • Protein Conformation
  • Protein Binding
  • Microsatellite Repeats
  • Humans
  • General Science & Technology
  • Gene Expression Regulation
  • Eukaryotic Cells
 

Citation

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Horton, C. A., Alexandari, A. M., Hayes, M. G. B., Marklund, E., Schaepe, J. M., Aditham, A. K., … Fordyce, P. M. (2023). Short tandem repeats bind transcription factors to tune eukaryotic gene expression. Science, 381(6664), eadd1250. https://doi.org/10.1126/science.add1250
Horton, Connor A., Amr M. Alexandari, Michael G. B. Hayes, Emil Marklund, Julia M. Schaepe, Arjun K. Aditham, Nilay Shah, et al. “Short tandem repeats bind transcription factors to tune eukaryotic gene expression.Science 381, no. 6664 (September 22, 2023): eadd1250. https://doi.org/10.1126/science.add1250.
Horton CA, Alexandari AM, Hayes MGB, Marklund E, Schaepe JM, Aditham AK, et al. Short tandem repeats bind transcription factors to tune eukaryotic gene expression. Science. 2023 Sep 22;381(6664):eadd1250.
Horton, Connor A., et al. “Short tandem repeats bind transcription factors to tune eukaryotic gene expression.Science, vol. 381, no. 6664, Sept. 2023, p. eadd1250. Pubmed, doi:10.1126/science.add1250.
Horton CA, Alexandari AM, Hayes MGB, Marklund E, Schaepe JM, Aditham AK, Shah N, Suzuki PH, Shrikumar A, Afek A, Greenleaf WJ, Gordân R, Zeitlinger J, Kundaje A, Fordyce PM. Short tandem repeats bind transcription factors to tune eukaryotic gene expression. Science. 2023 Sep 22;381(6664):eadd1250.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

September 22, 2023

Volume

381

Issue

6664

Start / End Page

eadd1250

Location

United States

Related Subject Headings

  • Transcription Factors
  • Saccharomyces cerevisiae
  • Protein Domains
  • Protein Conformation
  • Protein Binding
  • Microsatellite Repeats
  • Humans
  • General Science & Technology
  • Gene Expression Regulation
  • Eukaryotic Cells