A tissue-specific, naturally occurring human SNF2L variant inactivates chromatin remodeling

Orr Barak, Maribeth A. Lazzaro, Neil S. Cooch, David J. Picketts, Ramin Shiekhattar

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Mammalian genomes encode two imitation switch family chromatin remodeling proteins, SNF2H and SNF2L. In the mouse, SNF2H is expressed ubiquitously, whereas SNF2L expression is limited to the brain and gonadal tissue. This pattern of SNF2L expression suggests a critical role for SNF2L in neuronal physiology. Indeed, SNF2L was shown to promote neurite outgrowth as well as regulate the human engrailed homeotic genes, important regulators of brain development. Here we identify a novel splice variant of human SNF2L we call SNF2L+13, which contains a nonconserved in-frame exon within the conserved catalytic core domain of SNF2L. SNF2L+13 retains the ability to incorporate into multiprotein complexes; however, it is devoid of enzymatic activity. Most interestingly, unlike mouse SNF2L, human SNF2L is expressed ubiquitously, and regulation is mediated by isoform variation. The human SNF2L+13 null variant is predominant in non-neuronal tissue, whereas the human wild type active SNF2L isoform is expressed in neurons. Thus, like the mouse, active human SNF2L is limited to neurons and a few other tissues.

Original languageEnglish (US)
Pages (from-to)45130-45138
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number43
DOIs
StatePublished - Oct 22 2004
Externally publishedYes

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Chromatin Assembly and Disassembly
Chromatin
Tissue
Neurons
Brain
Protein Isoforms
Genes
Multiprotein Complexes
Physiology
Exons
Catalytic Domain
Switches
Homeobox Genes
Proteins
Genome

ASJC Scopus subject areas

  • Biochemistry

Cite this

A tissue-specific, naturally occurring human SNF2L variant inactivates chromatin remodeling. / Barak, Orr; Lazzaro, Maribeth A.; Cooch, Neil S.; Picketts, David J.; Shiekhattar, Ramin.

In: Journal of Biological Chemistry, Vol. 279, No. 43, 22.10.2004, p. 45130-45138.

Research output: Contribution to journalArticle

Barak, Orr ; Lazzaro, Maribeth A. ; Cooch, Neil S. ; Picketts, David J. ; Shiekhattar, Ramin. / A tissue-specific, naturally occurring human SNF2L variant inactivates chromatin remodeling. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 43. pp. 45130-45138.
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