A Sequence in the Drosophila H3-H4 Promoter Triggers Histone Locus Body Assembly and Biosynthesis of Replication-Coupled Histone mRNAs

Salzler, Harmony R.; Tatomer, Deirdre C.; Malek, Pamela Y.; McDaniel, Stephen L.; Orlando, Anna N.; Marzluff, William F.; Duronio, Robert J.

doi:10.1016/j.devcel.2013.02.014

Cited by 70 publications

(159 citation statements)

References 61 publications

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“…72,73 In addition, the sequence in histone pre-mRNA that binds U7 snRNP is not required for U7 snRNP recruitment to the Drosophila HLB. 74 Instead, we found that the C terminus of FLASH, likely together with Mxc, is necessary for recruitment of U7 snRNP to the HLB. 72 Thus, there are interactions among HLB components involved in assembling the HLB that are distinct from the interactions required for histone mRNA biosynthesis.…”

Section: Self-organization Of the Hlbmentioning

confidence: 63%

“…Indeed, we discovered a specific sequence in the Drosophila RD histone gene array that is necessary and sufficient to nucleate HLB assembly. 74 The Drosophila RD histone locus is composed of »100 copies of a tandemly arrayed 5kb sequence containing one copy of H1 and one copy of divergently transcribed H3/H4 and H2A/H2B gene pairs 1 (Fig. 3).…”

Section: Self-organization Of the Hlbmentioning

confidence: 99%

“…74 In addition to driving HLB assembly, the H3/H4 promoter sequence is required for efficient transcription from the H2A/H2B gene pair, even though the H2A/H2B pair contains intact promoters. 74 Together these results suggest that the H3/H4 promoter is required for HLB assembly, which in turn is critical for histone gene expression.…”

Section: Self-organization Of the Hlbmentioning

confidence: 99%

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Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

2017

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Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These mRNAs end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of the pre-mRNA. The genes for all 5 histone proteins are clustered in all metazoans and coordinately regulated with high levels of expression during S phase. Production of histone mRNAs occurs in a nuclear body called the Histone Locus Body (HLB), a subdomain of the nucleus defined by a concentration of factors necessary for histone gene transcription and premRNA processing. These factors include the scaffolding protein NPAT, essential for histone gene transcription, and FLASH and U7 snRNP, both essential for histone pre-mRNA processing. Histone gene expression is activated by Cyclin E/Cdk2-mediated phosphorylation of NPAT at the G1-S transition. The concentration of factors within the HLB couples transcription with pre-mRNA processing, enhancing the efficiency of histone mRNA biosynthesis. KEYWORDSCell cycle; Drosophila; histone genes; mRNA processing; nuclear bodyProper utilization of genetic information in eukaryotes requires extensive three-dimensional organization of the genome and its associated proteins within the nucleus. The basic unit of genome organization is the nucleosome, an octamer of two molecules of each of the four core histone proteins (H2A, H2B, H3 and H4) that packages »147 base pairs of DNA. In mammalian cells, approximately 4£10 8 molcules of each core histone must be synthesized during S phase of the cell cycle to package the newly replicated DNA. Defects in this process result in genome instability that can contribute to human pathologies like cancer. Histone protein synthesis results from a large increase in production at the beginning of S phase of equal amounts of mRNAs encoding the four core nucleosomal histones, as well as histone H1. This highly coordinated gene expression event is performed by a set of transcription and pre-mRNA processing factors unique to replication dependent (RD) histone mRNA biosynthesis that assemble into a nuclear body tightly associated with RD histone genes called the histone locus body (HLB). HLB formation involves a combination of ordered and stochastic assembly steps, and cell cycle regulated changes in the HLB occur to activate histone gene expression during S phase. Here we describe the history of how the HLB was discovered followed by a discussion of HLB assembly mechanism and how the HLB functions in RD histone mRNA biosynthesis.

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Section: Self-organization Of the Hlbmentioning

confidence: 63%

Section: Self-organization Of the Hlbmentioning

confidence: 99%

Section: Self-organization Of the Hlbmentioning

confidence: 99%

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Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

2017

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“…How HLBs (and other nuclear bodies) are formed remains a matter of debate, and models, including both highly hierarchical and random events, have been proposed (29,(37)(38)(39)(40)(41). In Drosophila, the initial step in HLB formation involves the recognition of chromatin at a specific site in the histone gene loci by a yet unidentified mechanism and subsequent recruitment of multi sex combs (Mxc), the Drosophila orthologue of NPAT, and FLASH, followed by the recruitment of the U7 snRNP and other pre-mRNA processing factors (42). At least some of these factors are recruited to HLBs prior to expressing histone genes, i.e.…”

mentioning

confidence: 99%

“…At least some of these factors are recruited to HLBs prior to expressing histone genes, i.e. in a manner independent of the presence of the histone pre-mRNAs (27,29,(42)(43)(44), indicating that the initial phase of HLB assembly is primarily driven by protein-protein interactions. Protein-RNA interactions that emerge following the initiation of transcription on histone genes likely contribute to formation of the fully developed and readily detectable HLBs (45).…”

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confidence: 99%

A Conserved Interaction That Is Essential for the Biogenesis of Histone Locus Bodies

Yang

Sabath

Kunduru

et al. 2014

Journal of Biological Chemistry

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Background: Proteins involved in expression of histone genes co-localize to discrete nuclear structures called histone locus bodies (HLBs). Results: Two main components of HLBs directly interact with each other through their C-terminal regions. Conclusion: Formation of HLBs depends on a subset of critical protein-protein interactions. Significance: Our work may help to understand the mechanisms that integrate transcription of histone genes with maturation of the nascent histone transcripts.

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Histones: Gene Organisation and Post‐translational Modification

Doenecke

2014

Encyclopedia of Life Sciences

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Histones are highly conserved basic proteins that form the major part of the protein moiety of eukaryotic chromosomes. Together with deoxyribonucleic acid (DNA) , they organise the repeat unit of chromatin, the nucleosome, which consists of a deoxyribonucleoprotein core particle and linker DNA connecting these core units. The core particle is composed of 147 nucleotide pairs of DNA and two copies of each of the four core histones H2A, H2B, H3 and H4. The DNA linking core particles is associated with one copy of a fifth histone type termed H1. The basal organisation of chromatin as a histone–DNA complex implies that histones functionally participate in the regulation of chromatin‐bound processes, such as transcription, DNA repair or DNA replication. Post‐translational modification of histone amino acid side chains or replacement of canonical histones by nonallelic variants and recognition of such modified sites by regulatory factors are key processes in modulating the functional organisation of chromatin. Key Concepts: The histone family of basic chromosome consists of five protein classes that organise together with DNA the nucleosome, the basic chromatin unit. Two copies of each of the four histones H2A, H2B, H3 and H4 form together with DNA the nucleosome core particle; linker DNA and histone H1 complete the nucleosome as the chromosomal repeat unit. The five canonical histones are extremely conserved proteins, and the nucleosome structure is essentially the same from unicellular to vertebrate species. Nonallelic variants of four of the five histones (the exception is H4) can replace the canonical isoforms, thereby mediating dynamic changes of chromatin structure and function. Histones are post‐translationally modified by, for example, acetylation of lysine residues, methylation of lysine or arginine residues and phosphorylation of hydroxyl groups in side chains of serine, threonine or tyrosine. Such modified side chains (and combinations thereof) provide interaction sites for binding of factors involved in chromatin‐bound processes. Histone H1 is also termed linker histones, because it interacts with the DNA linking nucleosome core particles. Yeast has just one type of H1‐like histones, whereas mammals have several nonallelic H1 variants. H1 is involved in the formation of higher order chromatin structures above the level of arrays of nucleosomes.

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A Sequence in the Drosophila H3-H4 Promoter Triggers Histone Locus Body Assembly and Biosynthesis of Replication-Coupled Histone mRNAs

Cited by 70 publications

References 61 publications

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

A Conserved Interaction That Is Essential for the Biogenesis of Histone Locus Bodies

Histones: Gene Organisation and Post‐translational Modification

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