Bryant B.,Constellation Pharmaceuticals
PLoS ONE | Year: 2012
In living cells, DNA is packaged along with protein and RNA into chromatin. Chemical modifications to nucleotides and histone proteins are added, removed and recognized by multi-functional molecular complexes. Here I define a new computational model, in which chromatin modifications are information units that can be written onto a one-dimensional string of nucleosomes, analogous to the symbols written onto cells of a Turing machine tape, and chromatin-modifying complexes are modeled as read-write rules that operate on a finite set of adjacent nucleosomes. I illustrate the use of this "chromatin computer" to solve an instance of the Hamiltonian path problem. I prove that chromatin computers are computationally universal - and therefore more powerful than the logic circuits often used to model transcription factor control of gene expression. Features of biological chromatin provide a rich instruction set for efficient computation of nontrivial algorithms in biological time scales. Modeling chromatin as a computer shifts how we think about chromatin function, suggests new approaches to medical intervention, and lays the groundwork for the engineering of a new class of biological computing machines. © 2012 Barbara Bryant.
Constellation Pharmaceuticals | Date: 2014-03-13
The present invention relates to compounds useful as inhibitors of one or more histone demethylses. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.
Constellation Pharmaceuticals | Date: 2015-05-08
Genentech and Constellation Pharmaceuticals | Date: 2014-09-04
Constellation Pharmaceuticals | Date: 2015-03-18
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.