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Two distinct nuclear localization signals in mammalian MSL1 regulate its function

Ruslan I Dmitriev1, Nikolay B Pestov, Mikhail I Shakhparonov

  • 1School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya, 117997, Moscow, Russia.

Journal of Cellular Biochemistry
|June 11, 2014
PubMed

Insights

The MSL1 protein, interacting with KAT8, controls histone H4 acetylation. This study identifies two nuclear localization signals (NLS) in MSL1, influencing its function in stem and cancer cells.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cell Biology

Background:

  • The MSL1 protein's role in regulating histone H4 K16 acetylation is known, particularly its interaction with KAT8.
  • The functional significance of different mammalian MSL1 protein isoforms remains unclear.
  • Histone acetylation patterns are crucial for gene regulation in both normal stem cells and cancer cells.

Purpose of the Study:

  • To investigate the functional significance of mammalian MSL1 isoforms.
  • To identify and characterize nuclear localization signals (NLS) within the MSL1 protein.
  • To understand how MSL1 isoforms and their NLS influence histone acetylation and protein interactions.

Main Methods:

  • Bioinformatics analysis to identify potential NLS sequences.
  • Cellular localization studies using immunofluorescence.
  • Co-immunoprecipitation assays to study protein-protein interactions.
  • Western blotting to assess histone H4 K16 acetylation levels.

Main Results:

  • A novel nuclear localization signal (NLS) was identified in MSL1, in addition to a previously known bipartite NLS.
  • MSL1 isoforms possessing both NLS were found to localize to specific sub-nuclear foci.
  • These MSL1 isoforms target the co-chaperone protein TTC4 within these foci.
  • All identified MSL1 isoforms demonstrated the ability to affect histone H4 K16 acetylation.
  • The presence of two NLS in MSL1 facilitates the in vivo activity of KAT8.

Conclusions:

  • MSL1 protein isoforms possess distinct localization patterns mediated by two NLS.
  • MSL1's interaction with TTC4 and its role in H4K16 acetylation are linked to its nuclear localization.
  • The dual NLS system in MSL1 is critical for mediating KAT8 activity and global histone acetylation.
  • These findings provide insights into MSL1 function in stem and cancer cells.
Keywords:
HISTONE ACETYLATIONKAT8MSL1NUCLEUSSUB-NUCLEAR LOCALIZATION

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