A tissue-specific, naturally occurring human SNF2L variant inactivates chromatin remodeling.
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.
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Orr
O
Barak
Maribeth A
MA
Lazzaro
Neil S
NS
Cooch
David J
DJ
Picketts
Ramin
R
Shiekhattar
D000251:Adenosine Triphosphatases / Q000737:chemistry; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D002845:Chromatography; D004262:DNA Restriction Enzymes / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017510:Protein Folding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014162:Transfection
D002843:Chromatin; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; C499336:SMARCA1 protein, human; C499335:Smarca1 protein, mouse; D014157:Transcription Factors; D004262:DNA Restriction Enzymes; D000251:Adenosine Triphosphatases