Related Experiment Video

Updated: Apr 19, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

9.0K

The transcriptional repressor ZBTB4 regulates EZH2 through a MicroRNA-ZBTB4-specificity protein signaling axis

Won Seok Yang1, Gayathri Chadalapaka2, Sung-Gook Cho3

  • 1Department of Environmental Health, University of Cincinnati, College of Medicine, 3223 Eden Ave., Cincinnati, OH 45267.

Neoplasia (New York, N.Y.)
|December 16, 2014
PubMed

Insights

ZBTB4, a transcriptional repressor, and EZH2 show an inverse relationship in breast cancer. Targeting the oncogenic miR-ZBTB4-Sp-EZH2 axis with agents like betulinic acid inhibits tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • ZBTB4 acts as a transcriptional repressor.
  • An inverse correlation exists between ZBTB4 and EZH2 expression in breast cancer patients.
  • EZH2 is a histone methyltransferase implicated in cancer progression.

Purpose of the Study:

  • To investigate the functional interaction between EZH2 and ZBTB4 in breast cancer.
  • To elucidate the regulatory network involving ZBTB4, EZH2, microRNAs, and Sp transcription factors.
  • To evaluate the therapeutic potential of targeting this network in breast cancer.

Main Methods:

  • Analysis of public microarray data from breast cancer patients.
  • Investigation of gene and protein expression in breast cancer cell lines.
  • RNA interference studies to assess the role of Sp proteins.
  • In vivo studies using a mouse model to evaluate therapeutic efficacy.

Main Results:

  • ZBTB4 directly suppresses EZH2 expression.
  • miR-106b and related microRNAs regulate ZBTB4.
  • Sp proteins (Sp1, Sp3, Sp4) are required for EZH2 expression and are suppressed by ZBTB4.
  • An Sp1-dependent EZH2 gene signature is associated with decreased patient survival.
  • Betulinic acid disrupts the miR-ZBTB4 signaling axis, down-regulates Sp proteins, and inhibits tumor growth and colonization in mice.

Conclusions:

  • EZH2 is reciprocally regulated by a novel network of Sp proteins, oncogenic microRNAs, and ZBTB4.
  • Modulation of this gene network represents a potential therapeutic strategy for breast cancer.
  • This signaling network may also be relevant for the treatment of other cancers.

More Related Videos

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

2.2K
Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes10:26

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes

Published on: January 16, 2015

8.9K

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.1K
Master Transcription Regulators02:23

Master Transcription Regulators

2.9K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.7K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
9.1K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
11.5K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
4.4K