REST and the RESTless: In Stem Cells and Beyond

Abstract

Since its original discovery as a negative regulator of neuronal differentiation, the repressor element (RE) -1 silencing transcription factor (REST), also known as the neuron-restrictive silencer factor, has been implicated in novel processes such as maintenance of embryonic stem cell pluripotency and self-renewal and regulation of mitotic fidelity in non-neural cells. REST expression and activity is tightly controlled by transcriptional and post-transcriptional mechanisms in a cell and developmental stage-specific manner and perturbations in its levels or function are associated with various pathological states. REST differentially influences target-gene expression through interaction with a wide variety of cellular cofactors in a context-dependent manner. However, the influence of the microenvironment on REST-mediated regulation of gene expression is poorly understood. This review will present our current understanding of REST signaling with a greater focus on its emerging ties with noncoding RNAs and novel interacting partners, as well as its roles in embryonic stem cell self-renewal, cellular plasticity and oncogenesis/tumor suppression.

Keywords:

• Down‘s syndrome
• embryonic stem cells
• medulloblastoma
• neural stem cells
• neuronal differentiation
• non-neural stem cells
• oncogenic activity
• pluripotency
• regulation of self-renewal
• REST/NRSF
• tumor-suppressor activity

Financial & competing interests disclosure

The author would like to thank the Children‘s Brain Tumor Foundation, the National Brain Tumor Foundation and the American Cancer Society Institutional Research Grant for grant support. Our work is also supported in part through the SPORE grant- P50CA127001 from the National Cancer Institute. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgement

The author is grateful to Sadhan Majumder for his editorial comments.

Additional information

Funding

The author would like to thank the Children‘s Brain Tumor Foundation, the National Brain Tumor Foundation and the American Cancer Society Institutional Research Grant for grant support. Our work is also supported in part through the SPORE grant- P50CA127001 from the National Cancer Institute. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.