The Direct and Individual Transcriptional Function of the Human Homodimeric and Heterodimeric Basic Helix-Loop-Helix Transcription Factors E47 and Scleraxis

  • 0Laboratorio de Biología Celular, Departamento de Investigación en Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City, Mexico.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology +

|

Abstract

The basic helix-loop-helix (bHLH) transcription factors (TFs) are essential in development and disease. Their function is regulated at multiple levels, including the structuring of homo- or heterodimeric forms among members of the family. Because most bHLH TFs have numerous dimerization partners, the commonly used overexpression or deletion experimental approaches in humans often generate results influenced by the altered regulatory balance of the TF network. To study the direct transcriptional role of two human bHLH TFs, we expressed them in an isolated system (yeast) with no additional tissue-specific bHLH TFs. The transcriptional effect was measured utilizing a GFP reporter controlled by human regulatory sequences containing different amounts of the bHLH TF consensus binding sites, the E-boxes. The individual transcriptional contributions of heterodimeric SCX-E47 or homodimeric E47 were compared over two human regulatory regions implicated in fibrosis: COL1A2 and TGFB1. Briefly, the heterodimeric SCX-E47 was the best activating form. The COL1A2 regulatory region showed the most significant transcriptional changes despite having fewer E-boxes (five) than the TGFB1 region (13). Finally, the context of the nearby TF binding sites and the core promoter was also relevant for the final individual transcriptional effect of the bHLH TFs tested.

Related Concept Videos

Master Transcription Regulators 02:23

6.9K

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...

General Transcription Factors 01:30

5.2K

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

Transcription Factors 02:16

75.7K

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

Co-activators and Co-repressors 02:04

7.3K

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...

RNA Polymerase II Accessory Proteins 02:36

9.1K

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...

Eukaryotic Transcription Activators 02:42

10.9K

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...