The role of mammalian histone H3 variants in gene regulation

• Applicant: Professorin Dr. Sandra Brigitte Hake
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2007 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 41898509

Eukaryotic organisms depend on complex and highly regulated mechanisms to activate or silence genes in response to a variety of stimuli. Epigenetic mechanisms alter the accessibility of proteins, such as transcription factors, to the DNA template to regulate transcriptional activity. Chromatin is build by the nucleosome core particles, which consist of DNA wrapped around an octameric unit of core histones (H2A, H2B, H3 and H4). Histones are subject to a diverse array of covalent post-translational modifications (PTMs) that might affect downstream cellular events by altering the structure of chromatin and/or generating a binding platform for effector proteins, which recognize the modification(s) and initiate events that lead to gene activation or silencing, as proposed in the histone code hypothesis. In some instances, specialized histone variants are found in place of the core histones to encode epigenetic information in defined or specialized nucleosome arrays. In this study we plan to address the question of whether mammalian histone H3 variants (H3.1, H3.2 and H3.3) are involved in the regulation of gene expression and ultimately in the establishment of epigenetic memory and cell fate determination, as proposed in our novel H3 barcode hypothesis (1). In this hypothesis, we speculate that H3.1 plays a role in constitutive heterochromatin formation, that H3.2 is found in facultative heterochromatin, and that H3.3 is involved in the transcriptional permissive state of euchromatin. Therefore, these H3 variants might play important roles in regulating gene expression.

• DFG Programme: Research Grants