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Charles David Allis
Charles David Allis (born March 22, 1951) is an American molecular biologist, and is currently the Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics at The Rockefeller University.
In pursuit of understanding the DNA-histone protein complex and the intricate system which allows for gene activation, the Allis lab focuses on chromatin signaling via histone modifications - acetylation, methylation and phosphorylation.
Allis is best known for deciphering regulatory mechanisms that impinge upon the fundamental repeating unit of chromatin and for identifying the responsible enzyme systems that govern the covalent modifications of histone proteins, the principal components that organize chromatin. Allis discovered the critical link, through histone acetyltransferase-containing transcriptional coactivators, between targeted histone acetylation and gene-specific transcriptional activation. In further studies, he linked histone phosphorylation events to mitosis and mitogen action, established a synergy between histone phosphorylation and acetylation events and elaborated the ‘histone code hypothesis’ (and extensions thereof), one of the most highly cited theories governing epigenetics. Implications of this research for human biology and human disease, notably cancer, are far-reaching and continuing at a remarkable pace.
==Research Significance ==
Chromatin is the physiological template of our genome. The packaging of DNA within chromatin, the orderly replication and distribution of chromosomes, the maintenance of genome integrity, and the regulated expression of genes depend upon the highly conserved histone proteins. Despite a longstanding appreciation of the primary structure of histones, various covalent modifications, and speculation about regulatory roles for histones in gene expression, the field was plagued for many years because of poor methods for histone/chromatin isolation, consequent histone/chromatin aggregation, and lack of any clear distinction between a basic uniform (repeating) chromatin structure versus a more heterogeneous array of histone modifications along the genome. It was generally believed that histone proteins were passive participants in packaging DNA into a more manageable form. Before Allis’ work, it was not appreciated that histone proteins might play an active role in dictating meaningful biological responses. No histone-modifying activity was known; thus, there was no reason to anticipate that transcription machinery might possess histone-modifying enzymatic functions.
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