Direct assessment of histone function using histone replacement

Corcoran, Emma Tung; Jacob, Yannick

doi:10.1016/j.tibs.2022.06.010

Cited by 6 publications

(4 citation statements)

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“…Drosophila melanogaster is the exemplar animal model organism for studying histone biology with many amenable natural features and engineered tools. Histone replacement platforms were developed by several groups and have been widely used to study different histone residues (Günesdogan et al 2010;McKay et al 2015;Zhang et al 2019;Corcoran and Jacob 2023). Each of these platforms has drawbacks that restrict the types of research questions that can be explored using them.…”

Section: Discussionmentioning

confidence: 99%

“…2015; Zhang et al . 2019; Corcoran and Jacob 2023). Each of these platforms has drawbacks that restrict the types of research questions that can be explored using them.…”

Section: Discussionmentioning

confidence: 99%

“…Drosophila melanogaster is an excellent experimental organism for manipulating the chromatin environment through direct mutation of histone genes (Corcoran and Jacob 2023). The organization of replication-dependent (RD) histone genes in Drosophila makes histone genetics tractable.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, a histone replacement platform was developed using CRISPR-Cas9-mediated engineering of the HisC locus (Figure 2D), replacing the endogenous histone gene array with two transgenic 5x histone gene arrays (Zhang et al, 2019;Figure 2E). These three gene replacement platforms have been used to greatly expand our understanding of metazoan histone residue function in the context of animal development (Günesdogan et al 2010;Hödl and Basler 2012;Pengelly et al 2013Pengelly et al , 2015McKay et al 2015;Yung et al 2015;Penke et al 2016;Graves et al 2016;Meers et al 2017Meers et al , 2018aArmstrong et al 2018Armstrong et al , 2019Copur et al 2018;Leatham-Jensen et al 2019;Zhang et al 2019;Koreski et al 2020;Finogenova et al 2020;Regadas et al 2021;Lindehell et al 2021;Crain et al 2022;Corcoran and Jacob 2023;Salzler et al 2023).…”

Section: Introductionmentioning

confidence: 99%

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Redesigning theDrosophilahistone gene cluster: An improved genetic platform for spatiotemporal manipulation of histone function

Crain,

Nevil,

Leatham-Jensen

et al. 2024

Preprint

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Mutating replication-dependent (RD) histone genes is an important tool for understanding chromatin-based epigenetic regulation. Deploying this tool in metazoan models is particularly challenging because RD histones in these organisms are typically encoded by many genes, often located at multiple loci. Such RD histone gene arrangements make the ability to generate homogenous histone mutant genotypes by site-specific gene editing quite difficult. Drosophila melanogaster provides a solution to this problem because the RD histone genes are organized into a single large tandem array that can be deleted and replaced with transgenes containing mutant histone genes. In the last ~15 years several different RD histone gene replacement platforms have been developed using this simple strategy. However, each platform contains weaknesses that preclude full use of the powerful developmental genetic capabilities available to Drosophila researchers. Here we describe the development of a newly engineered platform that rectifies many of these weaknesses. We used CRISPR to precisely delete the RD histone gene array (HisC), replacing it with a multifunctional cassette that permits site-specific insertion of either one or two synthetic gene arrays using selectable markers. We designed this cassette with the ability to selectively delete each of the integrated gene arrays in specific tissues using site-specific recombinases. We also present a method for rapidly synthesizing histone gene arrays of any genotype using Golden Gate cloning technologies. These improvements facilitate generation of histone mutant cells in various tissues at different stages of Drosophila development and provide an opportunity to apply forward genetic strategies to interrogate chromatin structure and gene regulation.

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Section: Discussionmentioning

confidence: 99%

“…2015; Zhang et al . 2019; Corcoran and Jacob 2023). Each of these platforms has drawbacks that restrict the types of research questions that can be explored using them.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%