Engineering chromatin states: Chemical and synthetic biology approaches to investigate histone modification function

Research output: Contribution to journalReviewpeer-review

Patterns of histone post-translational modifications (PTMs) and DNA modifications establish a landscape of chromatin states with regulatory impact on gene expression, cell differentiation and development. These diverse modifications are read out by effector protein complexes, which ultimately determine their functional outcome by modulating the activity state of underlying genes. From genome-wide studies employing high-throughput ChIP-Seq methods as well as proteomic mass spectrometry studies, a large number of PTMs are known and their coexistence patterns and associations with genomic regions have been mapped in a large number of different cell types. Conversely, the molecular interplay between chromatin effector proteins and modified chromatin regions as well as their resulting biological output is less well understood on a molecular level. Within the last decade a host of chemical approaches has been developed with the goal to produce synthetic chromatin with a defined arrangement of PTMs. These methods now permit systematic functional studies of individual histone and DNA modifications, and additionally provide a discovery platform to identify further interacting nuclear proteins. Complementary chemical- and synthetic-biology methods have emerged to directly observe and modulate the modification landscape in living cells and to readily probe the effect of altered PTM patterns on biological processes. Herein, we review current methodologies allowing chemical and synthetic biological engineering of distinct chromatin states in vitro and in vivo with the aim of obtaining a molecular understanding of histone and DNA modification function. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.

Original languageEnglish
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1839
Issue number8
Pages (from-to)644-656
Number of pages13
ISSN1874-9399
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

Bibliographical note

Funding Information:
B.F. gratefully acknowledges the Sandoz Family Foundation , the Swiss National Science Foundation (grant 31003A_149789 ) and EPFL for the financial support. S.K. is kindly supported by a fellowship of the Boehringer Ingelheim Fonds .

    Research areas

  • Chromatin-associated effectors, Designer chromatin, Epigenetics, Histone post-translational modifications, Protein chemistry, Synthetic biology

ID: 280237373