Skip header navigation

University of Stirling


Dr Kevin Petrie


Biological and Environmental Sciences University of Stirling, Stirling, FK9 4LA

Dr Kevin Petrie

About me


Isolation and Characterisation of Histone Deacetylase 9 and its Differentially Expressed Isoforms
University of London

Covalent modification of histones by reversible acetylation plays a key role in regulating gene expression. In a number of haematopoietic malignancies, disease pathogenesis has been associated with aberrant recruitment of histone deacetylases (HDACs) by a variety of oncoproteins leading to deregulated gene expression. Consequently, in recent years, the development of HDAC inhibitors for use in anti-cancer therapy has been a focus in clinical oncology research. However, the functional specificities that underpin the roles of various HDACs in oncogenesis are not understood. This thesis describes the isolation and sation of the class II HDAC, histone deacetylase 9, and the results of studies addressing its role in a variety of neoplastic diseases. The HDAC9 gene is highly complex, containing multiple promoters, and gives rise to alternatively spliced transcripts that encode protein isoforms with distinct biological activities. Isoforms of HDAC9 interact differentially with transcriptional repressors and corepressors such as BCL6, TEL and NCoR, display distinct cellular localisation patterns and are targeted by different post-translational modifications. Abnormal patterns of expression of HDAC9 isoforms have been detected in pre-B ALL cell lines and patient samples, including those harbouring the TEL-AML1 rearrangement. In addition, HDAC9 expression appeared to be deregulated in a number of non-haematological tumours, including breast and colon. Consistent with its expression in B cell tumours, HDAC9 protein is found to be expressed in normal spleen B cells, but is primarily confined to the marginal zone and at considerably lower levels than in B cell malignancies. These data might indicate a direct involvement of HDAC9 in some B cell malignancies and solid tumours and reinforce the need to explore a role for combination therapy involving specific HDAC inhibitors.

University of Stirling

Scroll back to the top