Innovation in gene regulation: The case of chromatin computation

Abstract

Chromatin regulation is understood to be one of the fundamental modes of gene regulation in eukaryotic cells. We argue that the basic proteins that determine the chromatin architecture constitute an evolutionary ancient layer of transcriptional regulation common to all three domains of life. We explore phylogenetically, sources of innovation in chromatin regulation, focusing on protein domains related to chromatin structure and function, demonstrating a step-wise increase of complexity in chromatin regulation. Building upon the highly conserved use of variants of chromosomal architectural proteins to distinguish chromosomal states, Eukarya secondarily acquired mechanisms for "writing" chemical modifications onto chromatin that constitute persistent signals. The acquisition of reader domains enabled decoding of these complex, signal combinations and a decoupling of the signal from immediate biochemical effects. We show how the coupling of reading and writing, which is most prevalent in crown-group Eukarya, could have converted chromatin into a powerful computational device capable of storing and processing more information than pure cis-regulatory networks.Key words: Chromatin, gene regulation, evolution Summary of Findings and Evolutionary HypothesisGene regulation in extant organisms is a complex adaptive system making use of a diversity of mechanisms to ensure that proteins and complementary macromolecular components are produced and maintained at functional levels in variable environments.In this contribution we focus on one key regulatory subsystem of the cell: chromatin regulation. We argue that chromatin functioned as general regulator of transcription in the primordial nucleus, and that a series of key molecular innovations has significantly expanded the regulatory scope of the cell. In this section we summarize the key empirical results of the paper. Sections 2 through 6 provide the empirical support for these claims. In section 7, we formulate an evolutionary Email addresses: sonja@bioinf.uni-leipzig.de (Sonja J. Prohaska), studla@bioinf.uni-leipzig.de (Peter F. Stadler), krakauer@santafe.edu (David C. Krakauer) hypothesis that seeks to explain our findings in terms of the evolution of proto-genetic regulation. We then interpret this evolutionary sequence in terms of increasing computational power by locating key stages of the evolutionary sequence within a formal model of computation. Since sections 2-6 are primarily concerned with presenting evidence, those interested in the conceptual development of the argument can focus on sections 7 and 8.Two variants of Chromosomal Architectural Proteins (ChAPs) are sufficient to define binary genomic, and potentially phenotypic, states. We show how extensions to this binary system lead to potential distinctions among an increasing number of genomic states, culminating in forms of control localized to specific sites in the genome, as illustrated for example by extant mammalian histone variants capable of differential expression and/or localization to r...

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