Research Article: Control of human testis-specific gene expression

Date Published: September 12, 2019

Publisher: Public Library of Science

Author(s): Jay C. Brown, Jean-Pierre Rouault.


As a result of decades of effort by many investigators we now have an advanced level of understanding about several molecular systems involved in the control of gene expression. Examples include CpG islands, promoters, mRNA splicing and epigenetic signals. It is less clear, however, how such systems work together to integrate the functions of a living organism. Here I describe the results of a study to test the idea that a contribution might be made by focusing on genes specifically expressed in a particular tissue, the human testis.

A database of 239 testis-specific genes was accumulated and each was examined for the presence of features relevant to control of gene expression. These include: (1) the presence of a promoter, (2) the presence of a CpG island (CGI) within the promoter, (3) the presence in the promoter of a transcription factor binding site near the transcription start site, (4) the level of gene expression, and (5) the above features in genes of testis-specific cell types such as spermatocyte and spermatid that differ in their extent of differentiation.

Of the 107 database genes with an annotated promoter, 56 were found to have one or more transcription factor binding sites near the transcription start site. Three of the binding sites observed, Pax-5, AP-2αA and GRα, stand out in abundance suggesting they may be involved in testis-specific gene expression. Compared to less differentiated testis-specific cells, genes of more differentiated cells were found to be (1) more likely to lack a CGI, (2) more likely to lack introns and (3) higher in expression level. The results suggest genes of more differentiated cells have a reduced need for CGI-based regulatory repression, reduced usage of gene splicing and a smaller set of expressed proteins.

Partial Text

The regulatory control of gene expression is a central feature of all living organisms. Beginning with the same genome sequence, features of differential gene expression collaborate to create the entire landscape of tissue and cell function including a life-long developmental program, pathways to maintain homeostasis and functions able to respond to environmental change. The crucial importance of gene regulatory control has made it a thoroughly-studied and familiar area of investigation. As a result we now know about central features of regulation including the role of promoters, CpG islands, epigenetic signaling, transcription factors, enhancers, structured chromosome domains, mRNA splicing and many others [1–7]. Lacking, however, is an appreciation of how the individual systems work together to produce smoothly functioning developmental and other programs. Are there features that are more fundamental in that they are expressed earlier in development or affect a greater number of tissues and cells? To what extent is the pathway of gene regulatory systems the same in different tissues? Are there pathways of gene expression that use some but not all of the gene regulatory features used in others? Are regulatory features deployed differently in developmental pathways compared to those involved in response to environmental change? The above questions and many related ones currently occupy investigators studying gene regulatory control.