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

2013 ◽  
Vol 24 (6) ◽  
pp. 623-634 ◽  
Author(s):  
Harmony R. Salzler ◽  
Deirdre C. Tatomer ◽  
Pamela Y. Malek ◽  
Stephen L. McDaniel ◽  
Anna N. Orlando ◽  
...  
Keyword(s):  
Histone Mrnas ◽  
Histone Locus Body ◽  
Histone Locus

scholarly journals Concentrating pre-mRNA processing factors in the histone locus body facilitates efficient histone mRNA biogenesis

2016 ◽  
Vol 213 (5) ◽  
pp. 557-570 ◽  
Author(s):  
Deirdre C. Tatomer ◽  
Esteban Terzo ◽  
Kaitlin P. Curry ◽  
Harmony Salzler ◽  
Ivan Sabath ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Mrna Processing ◽  
Histone Mrna ◽  
Histone Mrnas ◽  
Assembly Factor ◽  
U7 Snrnp ◽  
Histone Locus Body ◽  
Histone Locus ◽  
Processing Factors

The histone locus body (HLB) assembles at replication-dependent histone genes and concentrates factors required for histone messenger RNA (mRNA) biosynthesis. FLASH (Flice-associated huge protein) and U7 small nuclear RNP (snRNP) are HLB components that participate in 3′ processing of the nonpolyadenylated histone mRNAs by recruiting the endonuclease CPSF-73 to histone pre-mRNA. Using transgenes to complement a FLASH mutant, we show that distinct domains of FLASH involved in U7 snRNP binding, histone pre-mRNA cleavage, and HLB localization are all required for proper FLASH function in vivo. By genetically manipulating HLB composition using mutations in FLASH, mutations in the HLB assembly factor Mxc, or depletion of the variant histone H2aV, we find that failure to concentrate FLASH and/or U7 snRNP in the HLB impairs histone pre-mRNA processing. This failure results in accumulation of small amounts of polyadenylated histone mRNA and nascent read-through transcripts at the histone locus. Thus, the HLB concentrates FLASH and U7 snRNP, promoting efficient histone mRNA biosynthesis and coupling 3′ end processing with transcription termination.

scholarly journals Drosophila Symplekin localizes dynamically to the histone locus body and tricellular junctions

Nucleus ◽  
2014 ◽  
Vol 5 (6) ◽  
pp. 613-625 ◽  
Author(s):  
Deirdre C Tatomer ◽  
Lindsay F Rizzardi ◽  
Kaitlin P Curry ◽  
Alison M Witkowski ◽  
William F Marzluff ◽  
...  
Keyword(s):  
Histone Locus Body ◽  
Histone Locus

scholarly journals CDK-regulated phase separation seeded by histone genes ensures precise growth and function of Histone Locus Bodies

2019 ◽  
Author(s):  
Woonyung Hur ◽  
Marco Tarzia ◽  
Victoria E. Deneke ◽  
Esteban A. Terzo ◽  
Robert J. Duronio ◽  
...  
Keyword(s):  
Phase Separation ◽  
Gene Activation ◽  
Nuclear Body ◽  
Histone Mrnas ◽  
Histone Locus Bodies ◽  
Sex Combs ◽  
Zygotic Gene ◽  
Zygotic Gene Activation ◽  
And Function ◽  
Histone Locus

SummaryMany membrane-less organelles form through liquid-liquid phase separation, but how their size is controlled and whether size is linked to function remain poorly understood. The Histone Locus Body (HLB) is an evolutionarily conserved nuclear body that regulates the transcription and processing of histone mRNAs. Here, we show that Drosophila HLBs form through phase separation of the scaffold protein multi-sex combs (Mxc). The size of HLBs is controlled in a precise and dynamic manner that is dependent on the cell cycle and zygotic gene activation. Control of HLB growth is achieved by a mechanism integrating nascent mRNAs at the histone locus, which catalyzes phase separation, and the nuclear concentration of Mxc, which is controlled by the activity of cyclin-dependent kinases. Reduced Cdk2 activity results in smaller HLBs and the appearance of nascent, misprocessed histone mRNAs. Our experiments thus identify a mechanism linking nuclear body growth and size with gene expression.

scholarly journals Drosophila Prp40 localizes to the histone locus body and regulates gene transcription and development

2020 ◽  
Vol 133 (7) ◽  
pp. jcs239509 ◽  
Author(s):  
Silvia Prieto-Sánchez ◽  
Cristina Moreno-Castro ◽  
Cristina Hernández-Munain ◽  
Carlos Suñé
Keyword(s):  
Gene Transcription ◽  
Histone Locus Body ◽  
Histone Locus

scholarly journals Distinct self-interaction domains promote Multi Sex Combs accumulation in and formation of the Drosophila histone locus body

2015 ◽  
Vol 26 (8) ◽  
pp. 1559-1574 ◽  
Author(s):  
Esteban A. Terzo ◽  
Shawn M. Lyons ◽  
John S. Poulton ◽  
Brenda R. S. Temple ◽  
William F. Marzluff ◽  
...  
Keyword(s):  
Amino Acids ◽  
Nuclear Bodies ◽  
Confocal Imaging ◽  
Histone Mrna ◽  
Mrna Accumulation ◽  
Sex Combs ◽  
Histone Locus Body ◽  
Histone Locus ◽  
Multiple Domains

Nuclear bodies (NBs) are structures that concentrate proteins, RNAs, and ribonucleoproteins that perform functions essential to gene expression. How NBs assemble is not well understood. We studied the Drosophila histone locus body (HLB), a NB that concentrates factors required for histone mRNA biosynthesis at the replication-dependent histone gene locus. We coupled biochemical analysis with confocal imaging of both fixed and live tissues to demonstrate that the Drosophila Multi Sex Combs (Mxc) protein contains multiple domains necessary for HLB assembly. An important feature of this assembly process is the self-interaction of Mxc via two conserved N-terminal domains: a LisH domain and a novel self-interaction facilitator (SIF) domain immediately downstream of the LisH domain. Molecular modeling suggests that the LisH and SIF domains directly interact, and mutation of either the LisH or the SIF domain severely impairs Mxc function in vivo, resulting in reduced histone mRNA accumulation. A region of Mxc between amino acids 721 and 1481 is also necessary for HLB assembly independent of the LisH and SIF domains. Finally, the C-terminal 195 amino acids of Mxc are required for recruiting FLASH, an essential histone mRNA-processing factor, to the HLB. We conclude that multiple domains of the Mxc protein promote HLB assembly in order to concentrate factors required for histone mRNA biosynthesis.

scholarly journals The Cajal Body and Histone Locus Body

2010 ◽  
Vol 2 (7) ◽  
pp. a000653-a000653 ◽  
Author(s):  
Z. Nizami ◽  
S. Deryusheva ◽  
J. G. Gall
Keyword(s):  
Cajal Body ◽  
Histone Locus Body ◽  
Histone Locus

scholarly journals Drosophila Histone Locus Body assembly and function involves multiple interactions

2020 ◽  
Author(s):  
Kaitlin P. Koreski ◽  
Leila E. Rieder ◽  
Lyndsey M. McLain ◽  
William F. Marzluff ◽  
Robert J. Duronio
Keyword(s):  
Gene Expression ◽  
Repeat Unit ◽  
Gene Array ◽  
Homozygous Deletion ◽  
Histone Gene ◽  
Histone Genes ◽  
Histone Mrna ◽  
Histone Gene Expression ◽  
Histone Locus Body ◽  
Histone Locus

AbstractThe histone locus body (HLB) assembles at replication-dependent (RD) histone loci and concentrates factors required for RD histone mRNA biosynthesis. The D. melanogaster genome has a single locus comprised of ∼100 copies of a tandemly arrayed repeat unit containing one copy of each of the 5 RD histone genes. To determine sequence elements required for D. melanogaster HLB formation and histone gene expression, we used transgenic gene arrays containing 12 copies of the histone repeat unit that functionally complement loss of the ∼200 endogenous RD histone genes. A 12x histone gene array in which all H3-H4 promoters were replaced with H2a-H2b promoters does not form an HLB or express high levels of RD histone mRNA in the presence of the endogenous histone genes. In contrast, this same transgenic array is active in HLB assembly and RD histone gene expression in the absence of the endogenous RD histone genes and rescues the lethality caused by homozygous deletion of the RD histone locus. The HLB formed in the absence of endogenous RD histone genes on the mutant 12x array contains all known factors present in the wild type HLB including CLAMP, which normally binds to GAGA repeats in the H3-H4 promoter. These data suggest that multiple protein-protein and/or protein-DNA interactions contribute to HLB formation, and that the large number of endogenous RD histone gene copies sequester available factor(s) from attenuated transgenic arrays, thereby preventing HLB formation and gene expression.

scholarly journals Muscle wasted: a novel component of the Drosophila histone locus body required for muscle integrity

2010 ◽  
Vol 123 (16) ◽  
pp. 2697-2707 ◽  
Author(s):  
S. Bulchand ◽  
S. D. Menon ◽  
S. E. George ◽  
W. Chia
Keyword(s):  
Histone Locus Body ◽  
Histone Locus

scholarly journals Loss of Histone Locus Bodies in the Mature Hemocytes of Larval Lymph Gland Result in Hyperplasia of the Tissue in mxc Mutants of Drosophila

2020 ◽  
Vol 21 (5) ◽  
pp. 1586 ◽  
Author(s):  
Masanori Kurihara ◽  
Kouyou Komatsu ◽  
Rie Awane ◽  
Yoshihiro H. Inoue
Keyword(s):  
Ataxia Telangiectasia ◽  
Ectopic Expression ◽  
Mrna Levels ◽  
Lymph Glands ◽  
Histone Mrnas ◽  
Histone Locus Bodies ◽  
Responsible Gene ◽  
Sex Combs ◽  
Cycle Dependent ◽  
Histone Locus

Mutations in the multi sex combs (mxc) gene in Drosophila results in malignant hyperplasia in larval hematopoietic tissues, called lymph glands (LG). mxc encodes a component of the histone locus body (HLB) that is essential for cell cycle-dependent transcription and processing of histone mRNAs. The mammalian nuclear protein ataxia-telangiectasia (NPAT) gene, encoded by the responsible gene for ataxia telangiectasia, is a functional Mxc orthologue. However, their roles in tumorigenesis are unclear. Genetic analyses of the mxc mutants and larvae having LG-specific depletion revealed that a reduced activity of the gene resulted in the hyperplasia, which is caused by hyper-proliferation of immature LG cells. The depletion of mxc in mature hemocytes of the LG resulted in the hyperplasia. Furthermore, the inhibition of HLB formation was required for LG hyperplasia. In the mutant larvae, the total mRNA levels of the five canonical histones decreased, and abnormal forms of polyadenylated histone mRNAs, detected rarely in normal larvae, were generated. The ectopic expression of the polyadenylated mRNAs was sufficient for the reproduction of the hyperplasia. The loss of HLB function, especially 3′-end processing of histone mRNAs, is critical for malignant LG hyperplasia in this leukemia model in Drosophila. We propose that mxc is involved in the activation to induce adenosine deaminase-related growth factor A (Adgf-A), which suppresses immature cell proliferation in LG.

Sign in / Sign up

Export Citation Format

Share Document