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TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA

Adelene Y Tan1, Todd R Riley, Tristan Coady

  • 1Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 31, 2012
PubMed

Insights

The multifunctional protein TLS (FUS) regulates specific target genes by binding to single-stranded DNA sequences in their promoter regions. This discovery sheds light on TLS's role in gene expression, cancer, and neurological diseases.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The multifunctional protein TLS (FUS) is involved in crucial cellular processes like transcription and mRNA processing.
  • TLS is implicated in various diseases, including cancer and neurological disorders.
  • Understanding TLS target genes and recognition mechanisms is essential but largely unknown.

Purpose of the Study:

  • To identify genes regulated by TLS.
  • To elucidate the DNA sequence motifs recognized by TLS.
  • To understand how TLS binding influences gene expression.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) assays.
  • Promoter microarray analysis.
  • Computational sequence analysis.
  • In vitro DNA binding assays.

Main Results:

  • Identified several potential TLS target genes, with confirmed TLS occupancy.
  • Observed changes in target gene mRNA levels upon alteration of TLS levels, indicating both activation and repression.
  • Discovered specific DNA sequences (TLS response elements) enriched in TLS-bound fragments.
  • Demonstrated that purified TLS binds these sequences specifically in vitro, but only to single-stranded DNA.

Conclusions:

  • TLS regulates the expression of specific target genes.
  • TLS likely recognizes and binds to single-stranded DNA sequences within promoter regions.
  • This mechanism provides insight into TLS function in normal cellular processes and disease states.

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