Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2

Sci Rep. 2016 Nov 7:6:36699. doi: 10.1038/srep36699.

Abstract

Fascin 1 (FSCN1) is a cytoskeleton-associated protein recognized to function primarily in the regulation of cytoskeleton structure and formation of plasma membrane protrusions. Here we report a novel nuclear function for Fascin 1. Biochemical studies and genome wide localization using ChIP-seq identified phosphorylated Fascin 1 (pFascin) in complexes associated with transcription and that it co-localizes with histone H3 Lys4 trimethylation (H3K4me3) on chromatin. Gene expression profiling identified genes affected by Fascin 1 including SLC3A2, a gene encoding for a plasma membrane transporter that regulates intracellular amino acid levels. RbBP5, a subunit of the H3K4 histone methyltransferase (HMT) complex was found to interact with Fascin 1 supporting its role in H3K4me3 establishment at target genes. Moreover, we show that changes to SLC3A2 levels affect amino acid-mediated mTORC1 activation. These results reveal that Fascin 1 has a yet undiscovered nuclear function as an epigenetic modulator of genes essential for amino acid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins
  • Fusion Regulatory Protein 1, Heavy Chain / metabolism*
  • Gene Expression Regulation*
  • Gene Expression*
  • HEK293 Cells
  • Histones / metabolism
  • Humans
  • Microfilament Proteins / metabolism*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • TOR Serine-Threonine Kinases / metabolism
  • Transcriptome

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • FSCN1 protein, human
  • Fusion Regulatory Protein 1, Heavy Chain
  • Histones
  • Microfilament Proteins
  • Nuclear Proteins
  • RBBP5 protein, human
  • SLC3A2 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases

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