Cerebral Cortex Advance Access published online on April 15, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn051
Members of the NuRD Chromatin Remodeling Complex Interact with AUF1 in Developing Cortical Neurons
1 Neuroscience Program, 2 Department of Anatomy, Physiology and Genetics, School of Medicine, USUHS, Bethesda, MD 20814, USA, 3 Laboratory of Neurophysiology, NINDS, NIH, Bethesda, MD 20892, USA, 4 Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA
Address correspondence to Dr Denes V. Agoston, APG, USUHS, 4301 Jones Br Rd. Bethesda, MD 20814, USA. Email: vagoston{at}usuhs.edu.
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.
Key Words: cerebral cortex epigenetics gene expression histone acetylation neuronal differentiation progenitors
Cheol Lee and Andrea Gyorgy contributed equally to this work.