Science and Research

Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers

The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state. It does so while retaining the ability to respond dynamically to cellular signals. However, the mechanisms that guide SWI/SNF to specific genomic targets have remained elusive. Here we demonstrate that trans-acting long non-coding RNAs (lncRNAs) direct the SWI/SNF complex to cell type-specific enhancers. SWI/SNF preferentially binds lncRNAs and these predominantly bind DNA targets in trans. Together they localize to enhancers, many of which are cell type-specific. Knockdown of SWI/SNF- and enhancer-bound lncRNAs causes the genome-wide redistribution of SWI/SNF away from enhancers and a concomitant differential expression of spatially connected target genes. These lncRNA-SWI/SNF-enhancer networks support an enhancer hub model of SWI/SNF genomic targeting. Our findings reveal that lncRNAs competitively recruit SWI/SNF, providing a specific and dynamic layer of control over chromatin accessibility, and reinforcing their role in mediating enhancer activity and gene expression.

  • Oo, J. A.
  • Warwick, T.
  • Pálfi, K.
  • Lam, F.
  • McNicoll, F.
  • Prieto-Garcia, C.
  • Günther, S.
  • Cao, C.
  • Zhou, Y.
  • Gavrilov, A. A.
  • Razin, S. V.
  • Cabrera-Orefice, A.
  • Wittig, I.
  • Pullamsetti, S. S.
  • Kurian, L.
  • Gilsbach, R.
  • Schulz, M. H.
  • Dikic, I.
  • Müller-McNicoll, M.
  • Brandes, R. P.
  • Leisegang, M. S.

Keywords

  • *RNA, Long Noncoding/genetics/metabolism
  • *Enhancer Elements, Genetic/genetics
  • *Chromosomal Proteins, Non-Histone/metabolism/genetics
  • *Chromatin Assembly and Disassembly
  • Humans
  • *Transcription Factors/metabolism/genetics
  • Chromatin/metabolism/genetics
  • Animals
  • Gene Expression Regulation
  • Mice
Publication details
DOI: 10.1038/s41467-024-55539-6
Journal: Nat Commun
Pages: 131 
Number: 1
Work Type: Original
Location: UGMLC
Disease Area: General Lung and Other
Partner / Member: JLU, MPI-BN
Access-Number: 39747144

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