IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
- Chromatin structure and alternative splicing choices in G9a during cell differentiation.
Autor/es:
FISZBEIN A; QUAGLINO A; SCHOR IE; SREBROW A; KORNBLIHTT AR
Lugar:
Menoza
Reunión:
Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
In mammals G9a is the primary enzyme for mono- and dimethylation at Lys 9 of histone H3 (H3K9me1 and H3K9me2). There are two alternatively spliced mRNA variants of this gene, but their difference in function is still unknown. We have determined that, during neuronal and mammary cell differentiation, inclusion of the alternatively spliced exon 10 is increased. Since it is known that dynamic changes in intragenic chromatin structure could affect RNA polymerase II processivity or elongation rate, and thus modulate alternative splicing choices, we are currently studying the intragenic chromatin structure of G9a during cell differentiation. We have seen that treatment of neuronal differentiated cells with a DNA methylation inhibitor and with a histone hyper-acetylating drug revert the effect of differentiation on exon 10 inclusion, suggesting that an epigenetic component could be involved in this process. Furthermore, siRNA-mediated down regulation of G9a expression in neuronal differentiated cells changes the ratio between spliced variants, suggesting an important rol of G9a in regulating it ́s own splicing. We are currently analyzing the changes in DNA methylation that could be involved in the regulation of G9a alternative splicing and trying to determine which signal transduction pathways are specific to this mechanism.