A variety of chromatin remodeling complexes are thought to assist sequence-specific transcription factors from neuronal commitment to terminal maturation. The majority of the complexes described to date are expressed ubiquitously, suggesting that they have general transcriptional functions. Here we show that mammalian neurons have a specialized chromatin remodeling complex based on the presence of a neuro-specific splice variant of the recently discovered Lysine Specific Demethylase 1, LSD1. LSD1 was originally discovered as part of a co-repressor complex recruited by REST (also known as NRSF), a transcriptional silencer that controls expression of genes encoding the hallmarks of the neuronal phenotype outside the nervous system. The demethylase activity on Lys4 of histone H3 supports LSD1 epigenetic role in gene repression. LSD1 presents only one paralogue in the whole human genome, Amino Oxidase -flavin containing- domain 1 (AOF1). On this account, the event of alternative splicing, which occurs at higher frequency in singleton genes rather than in multigene families, could partially convey LSD1 functional diversification in the nervous system. We found that LSD1 mammalian transcripts can encompass several splice isoforms, some of which display a remarkable neuro-specific pattern of expression, while apparently retaining comparable demethylase activities. Neurospecific LSD1 isoforms arise at very early mouse embryonic stages and mature neurons display all the four identified LSD1 isoforms; in contrast, glial cells are devoid of the neuro-specific ones. Moreover the inclusion of the neuro-specific exon undergoes a dynamic modulation in an in vitro model of rat cortical neuron maturation. The progressive increase of neural LSD1 isoforms during maturation parallels the arousal of several synaptic components and neurotrophic factors setting the basis for LSD1 putative role in synaptic maturation.
Alternative splicing enhances lysine specific demethylase 1 (LSD1) epigenetic tuneability in the mammalian nervous system / C. Zibetti, A. Mattevi, C. Sala, E. Battaglioli. ((Intervento presentato al 4. convegno International congress on molecular mechanisms of neurodegeneration tenutosi a Milano nel 2009.
|Titolo:||Alternative splicing enhances lysine specific demethylase 1 (LSD1) epigenetic tuneability in the mammalian nervous system|
|Data di pubblicazione:||8-mag-2009|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Enti collegati al convegno:||Università degli Studi di Milano|
|Citazione:||Alternative splicing enhances lysine specific demethylase 1 (LSD1) epigenetic tuneability in the mammalian nervous system / C. Zibetti, A. Mattevi, C. Sala, E. Battaglioli. ((Intervento presentato al 4. convegno International congress on molecular mechanisms of neurodegeneration tenutosi a Milano nel 2009.|
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