Research

Neuronal Transcriptional Regulatory Mechanisms, The Prader-Willi Syndrome Chromosome Domain

Regulation of imprinted gene domains is controlled by cis-acting imprinting control regions that function in germline and/or early postzygotic development to establish active or inactive chromosomal domains, but the relationship to mechanisms of somatic gene expression is largely unknown. This study found that an entire approximately 2 Mb chromosomal imprinted domain associated with Prader-Willi syndrome (PWS) is coordinately regulated in somatic cells, and the transcription factor (TF) that controls this mechanism is Nuclear Respiratory Factor-1 (NRF-1).

Through bioinformatics, phylogenetic, functional reporter and mutation assays, as well as chromatin immunoprecipitation and siRNA studies this research showed that NRF-1 binding occurs in most of the known PWS region cis-regulatory elements and newly identified promoters and enhancers and that NRF-1 binding is essential for the high levels of neuronal transcription of these imprinted genes.

These findings enhance an understanding of molecular mechanisms by which TFs read and confer the epigenetic signal in somatic cells and provide mechanistic models for coordinate gene regulation in cis across active genomic domains consistent with a potential operon model.

Principal Investigator
Robert Nicholls, PhD

Last Update
August 14, 2010
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Last Update
August 14, 2010
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