Members of the NuRD chromatin remodeling complex interact with AUF1 in developing cortical neurons.
Chromatin remodeling plays an important role in coordinating gene expression during cortical development, however the identity of molecular complexes present in differentiating cortical neurons that mediate the process remains poorly understood. The A + U-rich element-binding factor 1 (AUF1) is a known regulator of messenger RNA stability and also acts as a transcription factor upon binding to AT-rich DNA elements. Here we show that AUF1 is specifically expressed in subsets of proliferating neural precursors and differentiating postmitotic neurons of the developing cerebral cortex. Moreover, AUF1 is coexpressed with histone deacetylase 1 (HDAC1) and metastasis-associated protein 2 (MTA2), members of the nucleosome remodeling and histone deacetylase complex. AUF1 specifically and simultaneously binds to HDAC1, MTA2, and AT-rich DNA element, its gene regulatory function is modulated by the extent of histone acetylation and in animals lacking AUF1, the composition of the complex is modified. These results suggest that AUF1 is involved in integrating genetic and epigenetic signals during cortical development through recruiting HDAC1 and MTA2 to AT-rich DNA elements.
Lee
Cheol
C
Neuroscience Program, School of Medicine, USUHS, Bethesda, MD 20814, USA.
Gyorgy
Andrea
A
Maric
Dragan
D
Sadri
Navid
N
Schneider
Robert J
RJ
Barker
Jeffery L
JL
Lawson
Michael
M
Agoston
Denes V
DV
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D002843:Chromatin / Q000201:enzymology / Q000502:physiology*; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism*; D016130:Immunophenotyping; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D008969:Molecular Sequence Data; D011247:Pregnancy; D051381:Rats; D014162:Transfection
D002843:Chromatin; D017931:DNA Primers; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630988:Hnrnpd protein, rat; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex