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Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases

Sandra S Johnson1, Cheng Zhang, Jody Fromm

  • 1Department of Biochemistry and Molecular Biology, Keck School of Medicine and the Norris Comprehensive Cancer Center, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.

Molecular Cell
|May 15, 2007
PubMed

Insights

Human Maf1 protein negatively regulates transcription by all nuclear RNA polymerases (Pols). Maf1 affects glioblastoma cell morphology and growth, suggesting it regulates cellular transformation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Most eukaryotic transcriptional regulators exhibit RNA polymerase (Pol)-selective activity.
  • The role of Maf1 in regulating transcription across different Pols is not fully understood.

Purpose of the Study:

  • To investigate the role of human Maf1 protein in regulating transcription by all three nuclear RNA polymerases.
  • To elucidate the mechanisms by which Maf1 influences transcription and cellular phenotypes.

Main Methods:

  • Assessing Maf1's impact on Pol I- and Pol III-dependent transcription in human glioblastoma cells.
  • Analyzing Maf1's interaction with the TATA binding protein (TBP) promoter and its effect on transcription factors.
  • Correlating Maf1 occupancy with initiation factors and Pol III on Pol III genes.
  • Evaluating phenotypic changes associated with altered Maf1 expression, including cell morphology, actin stress fibers, and anchorage-independent growth.

Main Results:

  • Human Maf1 protein negatively regulates transcription by RNA Pol I, Pol II, and Pol III.
  • Maf1 represses TBP transcription by targeting an Elk-1-binding site, with reciprocal occupancy.
  • Maf1 occupancy on Pol III genes is inversely correlated with TFIIIB and Pol III.
  • Reduced Maf1 expression alters cell morphology and increases actin stress fibers; Maf1 overexpression suppresses anchorage-independent growth.

Conclusions:

  • Maf1 acts as a global transcriptional repressor affecting all nuclear RNA polymerases.
  • Maf1's regulation of TBP and Pol III genes contributes to its control over cellular phenotypes.
  • Maf1 plays a significant role in regulating the transformation state of cells, impacting cell morphology and growth characteristics.

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