A Genetic Screen and Transcript Profiling Reveal a Shared Regulatory Program for<i>Drosophila</i>Linker Histone H1 and Chromatin Remodeler CHD1

Kavi, Harsh H.; Lu, Xingwu; Xu, Na; Bartholdy, Boris; Vershilova, Elena; Skoultchi, Arthur I.; Fyodorov, Dmitry V.

doi:10.1534/g3.115.016709

Cited by 4 publications

(6 citation statements)

References 47 publications

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“…5a). Interestingly, Chd1 and His1 genetically interact and share a large subset of regulatory targets in D. melanogaster in vivo 122 , which led to the speculation that CHD1 and H1 cooperate in the negative regulation of transcriptional elongation and/or repression of cryptic promoters in gene bodies.…”

Section: Molecular Mechanisms Of Actionmentioning

confidence: 99%

Emerging roles of linker histones in regulating chromatin structure and function

Fyodorov

Zhou

Skoultchi

et al. 2017

Nat Rev Mol Cell Biol

383

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Together with core histones, which make up the nucleosome, the linker histone (H1) is one of the five main histone protein families present in chromatin in eukaryotic cells. H1 binds to the nucleosome to form the next structural unit of metazoan chromatin, the chromatosome, which may help chromatin to fold into higher-order structures. Despite their important roles in regulating the structure and function of chromatin, linker histones have not been studied as extensively as core histones. Nevertheless, substantial progress has been made recently. The first near-atomic resolution crystal structure of a chromatosome core particle and an 11 Å resolution cryo-electron microscopy-derived structure of the 30 nm nucleosome array have been determined, revealing unprecedented details about how linker histones interact with the nucleosome and organize higher-order chromatin structures. Moreover, several new functions of linker histones have been discovered, including their roles in epigenetic regulation and the regulation of DNA replication, DNA repair and genome stability. Studies of the molecular mechanisms of H1 action in these processes suggest a new paradigm for linker histone function beyond its architectural roles in chromatin.

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Section: Molecular Mechanisms Of Actionmentioning

confidence: 99%

Emerging roles of linker histones in regulating chromatin structure and function

Fyodorov

Zhou

Skoultchi

et al. 2017

Nat Rev Mol Cell Biol

383

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“…Early studies of E(Pc) in Drosophila illustrated its critical role in chromatin regulation and we learned that E(Pc) is also involved in genomic imprint maintenance in Drosophila , likely through its role in heterochromatin maintenance (Joanis and Lloyd 2002). E(Pc) has been further highlighted for its important interactions (Table 2) with various genes and proteins involved in apoptosis and chromatin regulation, such as with ISWI (Imitation SWI), His1 (Histone H1), and Polycomb group genes (Ali and Bender 2004; Arancio et al 2010; Fullard and Baker 2015; Kavi et al 2015). As in yeast, E(Pc) is important in the cell cycle in Drosophila , where is it required during development for mitotic exit during the transition to a post-mitotic state (Flegel et al 2016).…”

Section: Comparative Studies Between Model Organisms Promote Functionmentioning

confidence: 99%

Critical genomic regulation mediated by Enhancer of Polycomb

Searle

Pillus

2017

Curr Genet

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Enhancer of Polycomb (EPC) was first identified for its contributions to development in Drosophila and was soon-thereafter purified as a subunit of the NuA4/TIP60 acetyltransferase complex. Since then, EPC has often been left in the shadows as an essential, yet non-catalytic subunit of NuA4/TIP60; however, its deep conservation and disease association make clear that it warrants additional attention. In fact, recent studies in yeast demonstrated that its Enhancer of Polycomb, Epl1, was just as important for gene expression and acetylation as is the catalytic subunit of NuA4. Despite its conservation, studies of EPC have often remained siloed between organisms. Here, our goal is to provide a cohesive view of the current state of the EPC literature as it stands among the major model organisms in which it has been studied. EPC is involved in multiple processes, beginning with its cardinal role in regulating global and targeted histone acetylation. EPC also frequently serves as an important interaction partner in these basic cellular functions, as well as in multicellular development, such as in hematopoiesis and skeletal muscle differentiation, and in human disease. Taken together, a unifying theme from these studies highlights EPC as a critical genomic regulator.

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“…Depending on the strength of the RNAi allele and temperature, adult viability is affected over a wide range, from a moderate decrease to complete lethality. We have recently identified a number of Drosophila His1 modifiers in a lethality-based genetic screen of EP misexpression alleles 20 . Among them, P{EP}Elba2 G17999 strongly suppresses lethality caused by moderate depletion of H1 by RNAi (to ~50% of wild-type levels).…”

Section: Resultsmentioning

confidence: 99%

“…Flies were maintained on standard corn meal, sugar and yeast medium with Tegosept at 18–27 °C as indicated. His1 RNAi and P{EP}Elba2 G17999 alleles are described elsewhere 5 20 . UAS-Elba2 , UAS-insv and UAS-hBEND6 transgenes are a generous gift of Eric Lai (Memorial Sloan Kettering Cancer Center).…”

Section: Methodsmentioning

confidence: 99%

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BEN domain protein Elba2 can functionally substitute for linker histone H1 in Drosophila in vivo

Kavi

et al. 2016

Sci Rep

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Metazoan linker histones are essential for development and play crucial roles in organization of chromatin, modification of epigenetic states and regulation of genetic activity. Vertebrates express multiple linker histone H1 isoforms, which may function redundantly. In contrast, H1 isoforms are not present in Dipterans, including D. melanogaster, except for an embryo-specific, distantly related dBigH1. Here we show that Drosophila BEN domain protein Elba2, which is expressed in early embryos and was hypothesized to have insulator-specific functions, can compensate for the loss of H1 in vivo. Although the Elba2 gene is not essential, its mutation causes a disruption of normal internucleosomal spacing of chromatin and reduced nuclear compaction in syncytial embryos. Elba2 protein is distributed ubiquitously in polytene chromosomes and strongly colocalizes with H1. In H1-depleted animals, ectopic expression of Elba2 rescues the increased lethality and ameliorates abnormalities of chromosome architecture and heterochromatin functions. We also demonstrate that ectopic expression of BigH1 similarly complements the deficiency of H1 protein. Thus, in organisms that do not express redundant H1 isoforms, the structural and biological functions performed by canonical linker histones in later development, may be shared in early embryos by weakly homologous proteins, such as BigH1, or even unrelated, non-homologous proteins, such as Elba2.

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A Genetic Screen and Transcript Profiling Reveal a Shared Regulatory Program forDrosophilaLinker Histone H1 and Chromatin Remodeler CHD1

Cited by 4 publications

References 47 publications

Emerging roles of linker histones in regulating chromatin structure and function

Emerging roles of linker histones in regulating chromatin structure and function

Critical genomic regulation mediated by Enhancer of Polycomb

BEN domain protein Elba2 can functionally substitute for linker histone H1 in Drosophila in vivo

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