Histones are proteins closely associated with DNA molecules. They are responsible for the structure of chromatin and play important roles in the regulation of gene expression, cell cycle progression and differentiation. Five types of histones have been identified : H1, H2A, H2B, H3 and H4. H1 and its homologous protein H5 are involved in higher order structures of chromatin. About 146 base pair DNA is wrapped around two copies of each of H2A, H2B, H3 and H4 forming the 'Nucleosome'.
The existing database on histones (http://research.nhgri.nih.gov/histones/) has information about Post Translational modifications (PTM), structures of histones and proteins containing the histone fold motif. However, there is no information on enzymes responsible for the PTMs and their relevance to various diseases. The Histone InfoBase contains detailed information on histones and their variants, PTMs, histone modifying enzymes and their relevance to different diseases. These Post Translational Modifications of specific amino acids impact on a variety of processes, like gene silencing, formation of heterochromatin , transcriptional regulation, DNA repair etc.
Primary databases like NCBI ,Swiss Prot, literature databases like OMIM, PubMed and PubMed Central along with recent publications have aided the extraction of relevant information found in this database. NCBI develops software tools for analyzing genome data. UniProtKB is a curated protein sequence database which provides a high level of annotation on protein function. The OMIM database is a catalog of human genes and genetic disorders. HPRD depicts protein interaction networks and disease associations. iHOP describes a complete network of genes along with literature citations. HUGO has approved over 24,000 human gene symbols and names. The Histone InfoBase contains links to all these databases.
How to Use the InfoBase:
The InfoBase can be viewed using Microsoft Internet Explorer with a screen resolution of 1024 by 768 pixels. However, you will encounter HTML Web pages that will try to run active content on your computer.To allow this blocked content to run, click the yellow bar. A content menu appears. Click "Allow Blocked Content." A dialog pop appears saying Allowing active content like Active X controls and script can be useful, but active content might also harm to your computer. Are you sure you want to allow this file to run active content?" Click the Yes button. The dialog box disappears and the yellow bar disappears. You can now access the active content on this page.
The InfoBase is subdivided into following categories for easy access.
Histone & Variants : Displays the list of histones and their variants, corresponding molecular weights and pI values. Clicking on a particular variant gives the gene details, chromosomal location, Online Mendelian Inheritance in Man (OMIM) entries and Human Genome Organisation (HUGO) entries.
Post translational modifications: Displays the list of variant specific PTM, the associated enzyme and its role. Clicking on the amino acid residue undergoing the modification displays details on the corresponding enzyme including relevance to disease.
Enzymes: Displays the list of enzymes that modify histones in Homo sapiens, their corresponding chromosomal location and the site of modification. Structures of enzymes are predicted using the SWISS-MODEL Workspace. They can be viewed using PyMOL software.
Advanced Search: Using Histone or Enzymes as two main key words.
Structure Visualization Freeware: Software such as RasMol, PyMOL, and Deep View SWISS-PDB viewer are freely available for download. They can be used for visualization of 3D structures of enzymes, their active sites as well as calculation of other parameters like inter atomic distances and Ramachandran plots.
Useful Links: Epigenome-Network of Excellence has been cited to keep abreast of the latest research. The SWISS-MODEL Workspace provides a pipeline of fully automated 3D structures. CREMOFAC is database reflecting the dynamic nature of chromatin facilitated by Remodeling Factors and provides in-depth information for the factors reported in the three widely studied mammals namely, human, mouse and rat.
Contact Us: Any queries/comments, kindly mail us at sgupta@actrec.gov.in . All user contributions can be addressed here.
Curators: Aarti Venkat, Meenakshi Sharma, Nikhil Gadewal.
Scientific Editors: Satyajeet Khare, Dr.Sanjay Gupta.
Advanced Centre for Treatment Research and Education in Cancer (ACTREC)
Cancer Research Institute, TATA MEMORIAL CENTRE, Kharghar, Navi Mumbai, INDIA