New lines of research on gene expression
The Parc Científic de Barcelona has for some months provided space for a new research group that studies the mechanisms regulating the ways in which genes are expressed in human cells, termed "Human and viral gene expression regulation in chromatin". The group is headed by Albert Jordan Vallès, titular scientist of the CSIC, who has worked at the Centre for Genomic Regulation (CRG: Centre de Regulació Genòmica) and recently joined the Barcelona Institute of Molecular Biology (IBMB-CSIC: Institut de Biologia Molecular de Barcelona). His laboratory is located on the first floor of the Hèlix Building.
Eukaryotic genetic material is in compact form inside the nuclei of cells, and it is made up of DNA and different types of proteins, among which are the histones. This set of elements makes up chromatin, which condenses to form the chromosome. Chromatin thus has a fundamental role in the regulation of gene expression and is, in principle, highly repressive for transcription, given that the association of DNA with proteins hinders the procession of the RNA polymerases. This is why there are a varied number of mechanisms that remodel chromatin and modify the histones. The different levels of compactness of the chromatin is associated—usually, but not always—with the degree of transcription shown by the genes in the corresponding areas.
The study of the organisation of chromatin as well as the functions and diverse forms of histones provides useful information that advances knowledge of the gene expression mechanisms and, hence, of the control of processes that facilitate cellular growth and function, as well as the replication of genetic material of the viruses and of virus infection capacity.
The group headed by Albert Jordan centres its research on the control of gene expression in human cells via chromatin organisation, its components, and its modifications. The group studies the role and the specificity of the isoforms of histone H1, types of protein found on the outside of the nucleosomes and that play a key role in the degree of compacting of genetic material. At present, the group has discovered some key characteristics of some isoforms of this histone, such as H1.2 and H1.4, which are decisive for the cellular proliferation of certain cell types, a finding that opens the path to the development of new therapeutic strategies to inhibit the growth of tumoral cells.
Finally, the team works with the Human Immunodeficiency Virus (HIV) promoter as a model for the investigation of the influence of chromatin organisation in the integration site on the expression of the virus. They have discovered that the capacity for RNA replication and, thus, for HIV infection, varies according to the site on the human genome where the genetic material is stored. They have also found that this location determines the ability of the virus to remain in the latent state, which makes its total elimination difficult in infected patients. The study of mechanisms of establishment or maintenance of viral latency should facilitate the design of new therapeutic strategies to improve the control of the development of the disease and, if possible, its eradication.