TY - JOUR

T1 - Engineering chromatin states

T2 - Chemical and synthetic biology approaches to investigate histone modification function

AU - Kilic, Sinan

AU - Fierz, Beat

N1 - 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 .

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - Chromatin-associated effectors

KW - Designer chromatin

KW - Epigenetics

KW - Histone post-translational modifications

KW - Protein chemistry

KW - Synthetic biology

UR - http://www.scopus.com/inward/record.url?scp=84904070796&partnerID=8YFLogxK

U2 - 10.1016/j.bbagrm.2014.04.016

DO - 10.1016/j.bbagrm.2014.04.016

M3 - Review

C2 - 24768924

AN - SCOPUS:84904070796

VL - 1839

SP - 644

EP - 656

JO - BBA Gene Regulatory Mechanisms

JF - BBA Gene Regulatory Mechanisms

SN - 1874-9399

IS - 8

ER -