Interrogating the function of metazoan histones using engineered gene clusters.

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Abstract

Histones and their posttranslational modifications influence the regulation of many DNA-dependent processes. Although an essential role for histone-modifying enzymes in these processes is well established, defining the specific contribution of individual histone residues remains a challenge because many histone-modifying enzymes have nonhistone targets. This challenge is exacerbated by the paucity of suitable approaches to genetically engineer histone genes in metazoans. Here, we describe a platform in Drosophila for generating and analyzing any desired histone genotype, and we use it to test the in vivo function of three histone residues. We demonstrate that H4K20 is neither essential for DNA replication nor for completion of development, unlike inferences drawn from analyses of H4K20 methyltransferases. We also show that H3K36 is required for viability and H3K27 is essential for maintenance of cellular identity but not for gene activation. These findings highlight the power of engineering histones to interrogate genome structure and function in animals.

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Journal

Journal ID (iso-abbrev): Dev. Cell

Title: Developmental cell

ISSN (Electronic): 1878-1551

ISSN (Print): 1534-5807

Publication date (Electronic): Feb 9 2015

Volume: 32

Issue: 3

Affiliations

[1 ] Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

[2 ] Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

[3 ] Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

[4 ] Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

[5 ] Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

[6 ] Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

[7 ] Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: duronio@med.unc.edu.

[8 ] Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: matera@unc.edu.

Article

Publisher Item ID: S1534-5807(14)00846-6 Mid ID: NIHMS659654

DOI: 10.1016/j.devcel.2014.12.025

PubMed ID: 25669886

SO-VID: 21bb85dd-3414-4cf5-bb1e-6089d2f108c8

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