Research

Profiling RE1/REST-mediated histone modifications in the human genome

Deyou Zheng^1,2 , Keji Zhao³ and Mark F Mehler^1,4

¹  Institute for Brain Disorders and Neural Regeneration, Department of Neurology, Rose F Kennedy Center for the Study of Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Morris Park Avenue, Bronx, NY 10461, USA

²  Department of Genetics and Neuroscience, Albert Einstein College of Medicine, Morris Park Avenue, Bronx, NY 10461, USA

³  Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institute of Health, Rockville Pike, Bethesda, MD 20892, USA

⁴  Departments of Neuroscience, and Psychiatry and Behavioral Sciences, Einstein Cancer Center, Albert Einstein College of Medicine, Morris Park Avenue, Bronx, NY 10461, USA

author email corresponding author email

Genome Biology 2009, 10:R9doi:10.1186/gb-2009-10-1-r9

Published:	27 January 2009

Abstract

Background

The transcriptional repressor REST (RE1 silencing transcription factor, also called NRSF for neuron-restrictive silencing factor) binds to a conserved RE1 motif and represses many neuronal genes in non-neuronal cells. This transcriptional regulation is transacted by several nucleosome-modifying enzymes recruited by REST to RE1 sites, including histone deacetylases (for example, HDAC1/2), demethylases (for example, LSD1), and methyltransferases (for example, G9a).

Results

We have investigated a panel of 38 histone modifications by ChIP-Seq analysis for REST-mediated changes. Our study reveals a systematic decline of histone acetylations modulated by the association of RE1 with REST (RE1/REST). By contrast, alteration of histone methylations is more heterogeneous, with some methylations increased (for example, H3K27me3, and H3K9me2/3) and others decreased (for example, H3K4me, and H3K9me1). Furthermore, the observation of such trends of histone modifications in upregulated genes demonstrates convincingly that these changes are not determined by gene expression but are RE1/REST dependent. The outcomes of REST binding to canonical and non-canonical RE1 sites were nearly identical. Our analyses have also provided the first direct evidence that REST induces context-specific nucleosome repositioning, and furthermore demonstrate that REST-mediated histone modifications correlate with the affinity of RE1 motifs and the abundance of RE1-bound REST molecules.

Conclusions

Our findings indicate that the landscape of REST-mediated chromatin remodeling is dynamic and complex, with novel histone modifying enzymes and mechanisms yet to be elucidated. Our results should provide valuable insights for selecting the most informative histone marks for investigating the mechanisms and the consequences of REST modulated nucleosome remodeling in both neural and non-neural systems.