Regulation of metabolism by the Mediator complex.

Dou Yeon Youn,Alus M Xiaoli,Jeffrey E Pessin,Fajun Yang

doi:10.1007/s41048-016-0031-6

Dou Yeon Youn, Alus M Xiaoli + Show 2 more

Open Access

https://doi.org/10.1007/s41048-016-0031-6

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Journal: Biophysics reports	Publication Date: Oct 1, 2016
Citations: 13	License type: CC BY 4.0

Affiliation: Albert Einstein College of Medicine

Abstract

The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

Highlights

Gene transcription in eukaryotic cells is orchestrated through extremely complicated processes and multiple steps, including initiation, elongation, and termination, with the initiation being the most studied regulation step of gene expression
Dysregulation of genes in the pathways controlling glucose and/or lipid metabolism is common in states of insulin resistance and type 2 diabetes (T2D), especially when patients are diagnosed with nonalcoholic fatty liver disease (NAFLD) or cardiovascular disease (Brown and Goldstein 2008; Oh et al 2013)
Currently there is no evidence that cAMP-regulated enhancer-binding protein (CREB) or Myb can directly bind to the Mediator complex, and depletion of some subunits such as MED15 or MED25 had no effect on Myb-dependent gene transcription in HEK293 cells (Yang et al 2004, 2006)

Summary

Introduction

Gene transcription in eukaryotic cells is orchestrated through extremely complicated processes and multiple steps, including initiation, elongation, and termination, with the initiation being the most studied regulation step of gene expression. The mediator kinase module behaves in a context-specific manner to either repress or activate transcription, depending on the transcription factors and/or target gene promoters (Nemet et al 2014).

Results

Conclusion