Essential genes in proximal 3L heterochromatin of Drosophila melanogaster

Schulze, Sandra; Sinclair, Donald A. R.; Silva, Elizabeth; Fitzpatrick, Kathleen A.; Singh, Manish Kumar; Lloyd, Vett K.; Morin, Karine; Kim, J.; Holm, David G.; Kennison, James A.; Honda, Barry M.

doi:10.1007/s004380000367

Cited by 30 publications

(30 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To determine the location of dSet1 along a genetic map of 3L centric heterochromatin (Schulze et al 2001;Fitzpatrick et al 2005; M. Syrzycka, unpublished data), we attempted to PCR-amplify the second and third exons of dSet1 using, as template, DNA isolated from embryos carrying deletions of 3L centric heterochromatin ( Figure 1A). In this way, we determined that dSet1 resides in the vicinity of the lethal 5/l(3)h5, lethal 7A/l(3)h7A, and lethal 7B/l (3)h7B loci ( Figure 1A).…”

Section: Immunostainingmentioning

confidence: 99%

dSet1 Is the Main H3K4 Di- and Tri-Methyltransferase ThroughoutDrosophilaDevelopment

Hallson

Hollebakken²,

Li³

et al. 2012

Genetics

View full text Add to dashboard Cite

In eukaryotes, the post-translational addition of methyl groups to histone H3 lysine 4 (H3K4) plays key roles in maintenance and establishment of appropriate gene expression patterns and chromatin states. We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a "global" or general H3K4 diand trimethyl HMT in Drosophila. Levels of H3K4 di-and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/ or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity of Set1 proteins is mediated through an evolutionarily conserved protein complex known as Complex of Proteins Associated with Set1 (COMPASS). We present biochemical evidence that dSet1 interacts with members of a putative Drosophila COMPASS complex and genetic evidence that these members are functionally required for H3K4 methylation. Taken together, our results suggest that dSet1 is responsible for the bulk of H3K4 di-and trimethylation throughout Drosophila development, thus providing a model system for better understanding the requirements for and functions of these modifications in metazoans.

show abstract

Section: Immunostainingmentioning

confidence: 99%

dSet1 Is the Main H3K4 Di- and Tri-Methyltransferase ThroughoutDrosophilaDevelopment

Hallson

Hollebakken²,

Li³

et al. 2012

Genetics

View full text Add to dashboard Cite

show abstract

“…The trxG genes are required to maintain activation of homeotic and other genes; many that have been molecularly characterized encode members of multimeric complexes with roles in transcriptional initiation and/or elongation. Typically, mutations in trxG genes suppress the phenotypes of mutations in PcG genes, whose function is to maintain the repressed state of homeotic genes (13-16) and other developmentally important genes like hedgehog (hh) (17), a gene required for cell signaling (18).As part of our work toward a functional annotation of heterochromatin of D. melanogaster (19), we characterized the verthandi (vtd) locus, a member of the trxG gene family with Suppressor of Polycomb [Su(Pc)] activity (11,20). The vtd locus also affects hh expression, as vtd mutations are dominant suppressors of Moonrat (Mrt), a dominant gain of function allele of hh (20,21).…”

mentioning

confidence: 99%

“…As part of our work toward a functional annotation of heterochromatin of D. melanogaster (19), we characterized the verthandi (vtd) locus, a member of the trxG gene family with Suppressor of Polycomb [Su(Pc)] activity (11,20). The vtd locus also affects hh expression, as vtd mutations are dominant suppressors of Moonrat (Mrt), a dominant gain of function allele of hh (20,21).…”

mentioning

confidence: 99%

The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein

Hallson

Syrzycka²,

Beck³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The cohesin complex is a key player in regulating cell division. Cohesin proteins SMC1, SMC3, Rad21, and stromalin (SA), along with associated proteins Nipped-B, Pds5, and EcoI, maintain sister chromatid cohesion before segregation to daughter cells during anaphase. Recent chromatin immunoprecipitation (ChIP) data reveal extensive overlap of Nipped-B and cohesin components with RNA polymerase II binding at active genes in Drosophila. These and other data strongly suggest a role for cohesion in transcription; however, there is no clear evidence for any specific mechanisms by which cohesin and associated proteins regulate transcription. We report here a link between cohesin components and trithorax group (trxG) function, thus implicating these proteins in transcription activation and/or elongation. We show that the Drosophila Rad21 protein is encoded by verthandi (vtd), a member of the trxG gene family that is also involved in regulating the hedgehog (hh) gene. In addition, mutations in the associated protein Nipped-B show similar trxG activity i.e., like vtd, they act as dominant suppressors of Pc and hh Mrt without impairing cell division. Our results provide a framework to further investigate how cohesin and associated components might regulate transcription.Hedgehog ͉ heterochromatin ͉ Nipped-B ͉ Polycomb ͉ cohesion I n eukaryotic mitosis, accurate chromosome segregation requires paired sister chromatids to attach to opposite spindle poles. Sister chromatids are held together by the cohesin protein complex, which consists of four core subunits, Rad21/SCC1, stromalin (SA) and structural maintenance of chromosome (SMC) proteins SMC1 and SMC3. A widely accepted model postulates that cohesin forms a ring-like structure via interaction of the N-and C-termini of Rad21 with a SMC1/SMC3 heterodimer. With the participation of SCC2/Nipped-B, SCC4, EcoI/Ctf7, and Pds5 proteins, sister-chromatid cohesion is maintained until the onset of mitosis. Cleavage of Rad21 and the resulting removal of cohesin then allow separation of sister chromatids in anaphase (see refs. 1-3 for reviews). Mutation of genes encoding these subunits leads to errors in chromosome segregation and aneuploidy, which are hallmarks of cancer and a leading cause of birth defects in humans (4).Given the highly conserved role for cohesin in sister chromatid cohesion, it was unexpected to discover that cohesin and associated proteins might also play a distinct, independent role in regulating gene expression. Reduction in Nipped-B expression in Drosophila affects expression of the cut and Ultrabithorax genes (5-7), and mutations in the human orthologue, NIPBL, result in Cornelia de Lange Syndrome (8). In zebrafish, mutations in rad21 or Smc3 affect embryonic runx gene transcription in heterozygous mutant animals without compromising cell division, suggesting that these proteins may have functions in transcription that are distinct from a mitotic role (9). Recently, Misulovin et al. observed extensive overlap of Nipped-B and cohesin components with RNA polymer...

show abstract

“…A small number of essential genes have been identified in autosomal heterochromatin of D. melanogaster (Hilliker and Holm 1975;Hilliker 1976;Marchant and Holm 1988a,b;Schulze et al 2001; reviewed by Coulthard et al 2003;Dimitri et al 2005;Fitzpatrick et al 2005). Their ability to function in this inactivating environment is puzzling, as is their repression when moved to distal sites within euchromatin (Wakimoto and Hearn 1990;Eberl et al 1993).…”

mentioning

confidence: 99%

Heterochromatic Genes in Drosophila: A Comparative Analysis of Two Genes

et al. 2006

View full text Add to dashboard Cite

Centromeric heterochromatin comprises 30% of the Drosophila melanogaster genome, forming a transcriptionally repressive environment that silences euchromatic genes juxtaposed nearby. Surprisingly, there are genes naturally resident in heterochromatin, which appear to require this environment for optimal activity. Here we report an evolutionary analysis of two genes, Dbp80 and RpL15, which are adjacent in proximal 3L heterochromatin of D. melanogaster. DmDbp80 is typical of previously described heterochromatic genes: large, with repetitive sequences in its many introns. In contrast, DmRpL15 is uncharacteristically small. The orthologs of these genes were examined in D. pseudoobscura and D. virilis. In situ hybridization and whole-genome assembly analysis show that these genes are adjacent, but not centromeric in the genome of D. pseudoobscura, while they are located on different chromosomal elements in D. virilis. Dbp80 gene organization differs dramatically among these species, while RpL15 structure is conserved. A bioinformatic analysis in five additional Drosophila species demonstrates active repositioning of these genes both within and between chromosomal elements. This study shows that Dbp80 and RpL15 can function in contrasting chromatin contexts on an evolutionary timescale. The complex history of these genes also provides unique insight into the dynamic nature of genome evolution.

show abstract

Essential genes in proximal 3L heterochromatin of Drosophila melanogaster

Cited by 30 publications

References 24 publications

dSet1 Is the Main H3K4 Di- and Tri-Methyltransferase ThroughoutDrosophilaDevelopment

dSet1 Is the Main H3K4 Di- and Tri-Methyltransferase ThroughoutDrosophilaDevelopment

The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein

Heterochromatic Genes in Drosophila: A Comparative Analysis of Two Genes

Contact Info

Product

Resources

About