Format

Send to

Choose Destination
Cell Rep. 2016 Mar 29;14(12):2797-808. doi: 10.1016/j.celrep.2016.02.063. Epub 2016 Mar 17.

Alternative Splicing of G9a Regulates Neuronal Differentiation.

Author information

1
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Ciudad Universitaria Pabellón II, C1428EHA Buenos Aires, Argentina.
2
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II, C1428EHA Buenos Aires, Argentina.
3
Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IFIBA-CONICET, Cuidad Universitaria Pabellón I, C1428EHA Buenos Aires, Argentina.
4
Instituto de Investigación en Biomedicina de Buenos Aires CONICET, Partner Institute of the Max Planck Society, C1425FQD Buenos Aires, Argentina.
5
Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IFIBA-CONICET, Cuidad Universitaria Pabellón I, C1428EHA Buenos Aires, Argentina; Centro de Microscopías Avanzadas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Cuidad Universitaria, C1428EHA Buenos Aires, Argentina.
6
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II, C1428EHA Buenos Aires, Argentina; Fundación Instituto Leloir, C1405BWE Buenos Aires, Argentina.
7
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Ciudad Universitaria Pabellón II, C1428EHA Buenos Aires, Argentina. Electronic address: ark@fbmc.fcen.uba.ar.

Abstract

Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10) through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10(+) isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation.

PMID:
26997278
DOI:
10.1016/j.celrep.2016.02.063
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center