IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Chromatin structure regulates alternative splicing in G9a and GLP during neuronal differentiation
Autor/es:
ANA FISZBEIN; ANA QUAGLINO; BRUNO G. BERARDINO; ANABELLA SREBROW; ALBERTO R KORNBLIHTT
Lugar:
Rosario
Reunión:
Congreso; XLIX Reunión Anual de la Sociendad Argentina de Investigación en Bioquímica y Biología; 2014
Resumen:
In mammals G9a and GLP are the primary enzymes for mono- and dimethylation at Lys 9 of histone H3 (H3K9me1 and H3K9me2). There are different alternatively spliced transcript variants of these genes, but their difference in function is still unknown. During in vitro and in vivo neuronal differentiation we have determined that inclusion of alternative spliced exons 10 in G9a and 12 in GLP are increased. Since it is known that dynamic changes in intragenic chromatin structure could affect RNA processivity modulating alternative splicing choices, we are currently studying the intragenic chromatin structure of G9a and GLP during cell differentiation. We have seen that treatment of mature neurons with a DNA methylation inhibitor and with a hyper-acetylating drug revert the effect of differentiation on the exon 10 inclusion, suggesting that an epigenetic component is involved in this process. Furthermore, treatment of neuronal differentiated cells with a siRNA against G9a or GLP change the ratio between spliced variants in G9a, suggesting an important rol of G9a in regulating it´s own splicing. However, the same knowdown have no effect on GLP alternative splicing pattern, pointing out a different splicing regulation between both genes during neuronal differentiation. Finally, we demonstrated that not only specific inhibition of G9a and GLP, but also knockdow of G9a cause the inhibition of neuronal differentation of N2a cell line.