IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A RELATION BETWEEN ALTERNATIVE SPLICING CHOICES AND CHROMATIN STRUCTURE IN NEURONAL DIFFERENTIATION
Autor/es:
FISZBEIN A; SCHOR IE; PETRILLO E; KORNBLIHTT AR
Lugar:
Potrero de los Funes
Reunión:
Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2011
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
RNA polymerase II elongation rates modulate
alternative splicing choices and affect the timing at which nascent pre-mRNA
splice sites and regulatory sequences are presented to the spliceosome. This is
relevant in regulation of endogenous alternative splicing events by dynamic
changes in intragenic chromatin structure that could affect RNA processivity or
elongation rate. Using the alternative exon 18 of the NCAM gene as a model, we
have shown that neuronal differentiation triggers transcription-repressive
intragenic histone modifications (such as H3K9me2 and H3K27me3) in the NCAM
gene, correlating with an increase of its alternative exon 18 inclusion. This
alternative exon inclusion determines the expression of the NCAM 180 isoform,
typical of mature and stable synapses. We study this regulation using
DMSO-induced differentiation of N2a cells, a murine neuronal cell line.
Treatment of differentiated N2a cells with a DNA methylation inhibitor reverts
the effect of differentiation on the exon 18 inclusion, whereas treatment with
a hyper-acetylating drug has the opposite effect. To extend the analysis to
other alternative splicing events, we used available ChIP-seq data to search
genes with correlated modulation of both histone marks and AS patterns during
neuronal differentiation, and selected the Tcf7l2 and the fibronectin genes. This
regulation could be an example of chromatin-dependent alternative splicing
modulation associated with development.