Give me your genomic position, I will tell you who you are!
a) Schematic representation of the nucleosome showing the place of the H1 and core histones relative to DNA.
b) Schema of the H1 subtypes distribution on DNA regulatory sequences.
June 6, 2013
The Robert Schneider team at the IGBMC, in collaboration with the Bas van Steensel group at the Netherlands Cancer Institute, has just completed the first genomic mapping of the linker histones H1 in humans. This sheds a new light on the genome wide distribution of this family of proteins and highlight their role in nuclear architecture. Their findings are published on June 6th in Cell Reports.
Molecules of compacting!
Histones, present in the nucleus of cells, are the major protein component of chromosomes. A structure formed by 2 copies of 4 histones (H3, H4, H2A, H2B) associates with DNA to form the nucleosome, the building block of chromatin: DNA is wrapped around these core histones like thread around a spool (figure a). A 5th histone, the linker histone H1 binds the DNA winding on this spool and stabilizes it by promoting further compaction of the nucleosomes. Different degrees of chromatin compaction, finely orchestrated during the cell life, can, indeed, enable effective organization of DNA in the small space of the cellular nucleus. For example, DNA must be unrolled to be accessible to the enzyme that copies it before cell division.
Histone H1, a neglected family.
The linker histones are those in which the researchers were interested in. There are five somatic* H1 subtypes or isoforms in humans: from H1.1 to H1.5. The functional role of H1 in chromatin, and in particular of its isoforms, remains elusive; core histones were so far grabbing the most attention of scientists. Annalizo Izzo has addressed this issue now, by mapping the genomic distribution of the 5 somatic H1 subtypes in human cells. She identified specifc DNA regions and nuclear subcompartments associated with H1 subtypes. Many new data are thus available to the scientific community.
Towards a better understanding of the function of isoforms ...
The results of this study show that, in general, the linker histones H1 are depleted from certain genomic regions (see Figure b) that are involved in the regulation of DNA dependent-processes (transcription, DNA replication). The isoform H1.1 shows, in terms of distribution, a binding profile distinct from his peers, suggesting a different function. In addition this study points towards a potential role for H1 subtypes in the three-dimensional genome organization. Specific mutations in H1 family proteins have been identified in several types of cancers. For instance, there is an association between the colon cancer and an altered expression of histone H1.5. Thus elucidation of the principles that promote the binding of H1 subtypes to chromatin will substantially increase our understanding of many diseases and provide new opportunities for the prevention and treatment of cancer.