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Sidorenko, D. S., Sidorenko, I. A., Zykova, T. Y., Goncharov, F. P., Larsson, J. & Zhimulev, I. F. (2019). Molecular and genetic organization of bands and interbands in the dot chromosome of Drosophila melanogaster. Chromosoma, 128(2), 97-117
Open this publication in new window or tab >>Molecular and genetic organization of bands and interbands in the dot chromosome of Drosophila melanogaster
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2019 (English)In: Chromosoma, ISSN 0009-5915, E-ISSN 1432-0886, Vol. 128, no 2, p. 97-117Article in journal (Refereed) Published
Abstract [en]

The fourth chromosome smallest in the genome of Drosophila melanogaster differs from other chromosomes in many ways. It has high repeat density in conditions of a large number of active genes. Gray bands represent a significant part of this polytene chromosome. Specific proteins including HP1a, POF, and dSETDB1 establish the epigenetic state of this unique chromatin domain. In order to compare maps of localization of genes, bands, and chromatin types of the fourth chromosome, we performed FISH analysis of 38 probes chosen according to the model of four chromatin types. It allowed clarifying the dot chromosome cytological map consisting of 16 loose gray bands, 11 dense black bands, and 26 interbands. We described the relation between chromatin states and bands. Open aquamarine chromatin mostly corresponds to interbands and it contains 5UTRs of housekeeping genes. Their coding parts are embedded in gray bands substantially composed of lazurite chromatin of intermediate compaction. Polygenic black bands contain most of dense ruby chromatin, and also some malachite and lazurite. Having an accurate map of the fourth chromosome bands and its correspondence to physical map, we found that DNase I hypersensitivity sites, ORC2 protein, and P-elements are mainly located in open aquamarine chromatin, while element 1360, characteristic of the fourth chromosome, occupies band chromatin types. POF and HP1a proteins providing special organization of this chromosome are mostly located in aquamarine and lazurite chromatin. In general, band organization of the fourth chromosome shares the features of the whole Drosophila genome.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Drosophila, Polytene chromosomes, Dot chromosome, Chromatin types, Bands, Interbands
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-160286 (URN)10.1007/s00412-019-00703-x (DOI)000469209900003 ()31041520 (PubMedID)
Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-06-17Bibliographically approved
Sidorenko, D. S., Zykova, T. Y., Khoroshko, V. A., Pokholkova, G. ,., Demakov, S. A., Larsson, J., . . . Zhimulev, I. F. (2019). Polytene chromosomes reflect functional organization of the Drosophila genome. Vavilovski Zhurnal Genetiki i Selektsii, 23(2), 148-153
Open this publication in new window or tab >>Polytene chromosomes reflect functional organization of the Drosophila genome
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2019 (English)In: Vavilovski Zhurnal Genetiki i Selektsii, ISSN 2500-0462, Vol. 23, no 2, p. 148-153Article, review/survey (Refereed) Published
Abstract [en]

Polytene chromosomes of Drosophila melanogaster are a convenient model for studying interphase chromosomes of eukaryotes. They are giant in size in comparison with diploid cell chromosomes and have a pattern of cross stripes resulting from the ordered chromatid arrangement. Each region of polytene chromosomes has a unique banding pattern. Using the model of four chromatin types that reveals domains of varying compaction degrees, we were able to correlate the physical and cytological maps of some polytene chromosome regions and to show the main properties of genetic and molecular organization of bands and interbands, that we describe in this review. On the molecular map of the genome, the interbands correspond to decompacted aquamarine chromatin and 5' ends of ubiquitously active genes. Gray bands contain lazurite and malachite chromatin, intermediate in the level of compaction, and, mainly, coding parts of genes. Dense black transcriptionally inactive bands are enriched in ruby chromatin. Localization of several dozens of interbands on the genome molecular map allowed us to study in detail their architecture according to the data of whole genome projects. The distribution of proteins and regulatory elements of the genome in the promoter regions of genes localized in the interbands shows that these parts of interbands are probably responsible for the formation of open chromatin that is visualized in polytene chromosomes as interbands.Thus, the permanent genetic activity of interbands and gray bands and the inactivity of genes in black bands are the basis of the universal banding pattern in the chromosomes of all Drosophila tissues. The smallest fourth chromosome of Drosophila with an atypical protein composition of chromatin is a special case. Using the model of four chromatin states and fluorescent in situ hybridization, its cytological map was refined and the genomic coordinates of all bands and interbands were determined. It was shown that, in spite of the peculiarities of this chromosome, its band organization in general corresponds to the rest of the genome. Extremely long genes of different Drosophila chromosomes do not fit the common scheme, since they can occupy a series of alternating bands and interbands (up to nine chromosomal structures) formed by parts of these genes.

Place, publisher, year, edition, pages
Russian Academy of Sciences, 2019
Keywords
Drosophila melanogaster, polytene chromosomes, interphase chromosomes, four chromatin state del, fluorescent in situ hybridization, genetic organization, bands and interbands of chromosomes, MAKOV SA, 1993, MOLECULAR & GENERAL GENETICS, V238, P437 oroshko Varvara A., 2016, PLOS ONE, V11, dorenko D. S., 2018, Chromosome 2018: International Conference, August 20-24, 2018, Novosibirsk, ssia, P75 imulev I. F., 2016, DOKLADY BIOCHEMISTRY AND BIOPHYSICS, V466, P57 kova T. Yu., 2019, Dokl. Biochem. Biophys., V485, P1 rsson J, 2004, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
National Category
Genetics
Identifiers
urn:nbn:se:umu:diva-158766 (URN)10.18699/VJ19.474 (DOI)000462989500005 ()
Available from: 2019-05-13 Created: 2019-05-13 Last updated: 2019-05-13Bibliographically approved
Kim, M., Faucillion, M.-L. & Larsson, J. (2018). RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation. PLoS Genetics, 14(12), Article ID e1007842.
Open this publication in new window or tab >>RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation
2018 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 14, no 12, article id e1007842Article in journal (Refereed) Published
Abstract [en]

In Drosophila melanogaster, the male-specific lethal (MSL) complex plays a key role in dosage compensation by stimulating expression of male X-chromosome genes. It consists of MSL proteins and two long noncoding RNAs, roX1 and roX2, that are required for spreading of the complex on the chromosome and are redundant in the sense that loss of either does not affect male viability. However, despite rapid evolution, both roX species are present in diverse Drosophilidae species, raising doubts about their full functional redundancy. Thus, we have investigated consequences of deleting roX1 and/or roX2 to probe their specific roles and redundancies in Dmelanogaster. We have created a new mutant allele of roX2 and show that roX1 and roX2 have partly separable functions in dosage compensation. In larvae, roX1 is the most abundant variant and the only variant present in the MSL complex when the complex is transmitted (physically associated with the X-chromosome) in mitosis. Loss of roX1 results in reduced expression of the genes on the X-chromosome, while loss of roX2 leads to MSL-independent upregulation of genes with male-biased testis-specific transcription. In roX1 roX2mutant, gene expression is strongly reduced in a manner that is not related to proximity to high-affinity sites. Our results suggest that high tolerance of mis-expression of the X-chromosome has evolved. We propose that this may be a common property of sex-chromosomes, that dosage compensation is a stochastic process and its precision for each individual gene is regulated by the density of high-affinity sites in the locus.

Place, publisher, year, edition, pages
Public Library Science, 2018
National Category
Genetics
Identifiers
urn:nbn:se:umu:diva-155778 (URN)10.1371/journal.pgen.1007842 (DOI)000455099000025 ()30532158 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2014.0018Swedish Research Council, 2016-03306Swedish Cancer Society, CAN 2017/342
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved
Kim, M., Ekhteraei-Tousi, S., Lewerentz, J. & Larsson, J. (2018). The X-linked 1.688 satellite in Drosophila melanogaster promotes specific targeting by Painting of Fourth. Genetics, 208(2), 623-632
Open this publication in new window or tab >>The X-linked 1.688 satellite in Drosophila melanogaster promotes specific targeting by Painting of Fourth
2018 (English)In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 208, no 2, p. 623-632Article in journal (Refereed) Published
Abstract [en]

Repetitive DNA, represented by transposons and satellite DNA, constitutes a large portion of eukaryotic genomes, being the major component of constitutive heterochromatin. There is a growing body of evidence that it regulates several nuclear functions including chromatin state and the proper functioning of centromeres and telomeres. The 1.688 satellite is one of the most abundant repetitive sequences in Drosophila melanogaster, with the longest array being located in the pericentromeric region of the X-chromosome. Short arrays of 1.688 repeats are widespread within the euchromatic part of the X-chromosome, and these arrays were recently suggested to assist in recognition of the X-chromosome by the dosage compensation male-specific lethal complex. We discovered that a short array of 1.688 satellite repeats is essential for recruitment of the protein POF to a previously described site on the X-chromosome (PoX2) and to various transgenic constructs. On an isolated target, i.e., an autosomic transgene consisting of a gene upstream of 1.688 satellite repeats, POF is recruited to the transgene in both males and females. The sequence of the satellite, as well as its length and position within the recruitment element, are the major determinants of targeting. Moreover, the 1.688 array promotes POF targeting to the roX1-proximal PoX1 site in trans Finally, binding of POF to the 1.688-related satellite-enriched sequences is conserved in evolution. We hypothesize that the 1.688 satellite functioned in an ancient dosage compensation system involving POF targeting to the X-chromosome.

Place, publisher, year, edition, pages
Bethesda: The Genetics Society, 2018
Keywords
Drosophila melanogaster, Painting of fourth, dosage compensation, epigenetics, heterochromatin
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-144381 (URN)10.1534/genetics.117.300581 (DOI)000423563400012 ()29242291 (PubMedID)
Available from: 2018-02-01 Created: 2018-02-01 Last updated: 2018-06-09Bibliographically approved
Faucillion, M.-L. & Larsson, J. (2015). Increased expression of X-linked genes in mammals is associated with a higher stability of transcripts and an increased ribosome density. Genome Biology and Evolution, 7(4), 1039-1052
Open this publication in new window or tab >>Increased expression of X-linked genes in mammals is associated with a higher stability of transcripts and an increased ribosome density
2015 (English)In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 7, no 4, p. 1039-1052Article in journal (Refereed) Published
Abstract [en]

Mammalian sex chromosomes evolved from the degeneration of one homolog of a pair of ancestral autosomes, the proto-Y. This resulted in a gene dose imbalance that is believed to be restored (partially or fully) through up-regulation of gene expression from the single active X-chromosome in both sexes by a dosage compensatory mechanism. We analyzed multiple genome-wide RNA stability datasets and found significantly longer average half-lives for X-chromosome transcripts than for autosomal transcripts in various human cell lines, both male and female, and in mice. Analysis of ribosome profiling data shows that ribosome density is higher on X-chromosome transcripts than on autosomal transcripts in both humans and mice, suggesting that the higher stability is causally linked to a higher translation rate. Our results and observations are in accordance with a dosage compensatory upregulation of expressed X-linked genes. We therefore propose that differential mRNA stability and translation rates of the autosomes and sex chromosomes contribute to an evolutionarily conserved dosage compensation mechanism in mammals.

Place, publisher, year, edition, pages
Oxford University Press, 2015
Keywords
dosage compensation, RNA stability, sex chromosomes, RNA half-life, ribosome density
National Category
Genetics Evolutionary Biology
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-101245 (URN)10.1093/gbe/evv054 (DOI)000355148800010 ()25786432 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2015-03-26 Created: 2015-03-26 Last updated: 2018-06-07Bibliographically approved
Lindehell, H., Kim, M. & Larsson, J. (2015). Proximity ligation assays of protein and RNA interactions in the male-specific lethal complex on Drosophila melanogaster polytene chromosomes. Chromosoma, 124(3), 385-395
Open this publication in new window or tab >>Proximity ligation assays of protein and RNA interactions in the male-specific lethal complex on Drosophila melanogaster polytene chromosomes
2015 (English)In: Chromosoma, ISSN 0009-5915, E-ISSN 1432-0886, Vol. 124, no 3, p. 385-395Article in journal (Refereed) Published
Abstract [en]

In Drosophila, the male-specific lethal (MSL) complex specifically targets the male X chromosome and participates in a twofold increase in expression output leading to functional dosage compensation. The complex includes five proteins and two non-coding RNAs (ncRNAs). A number of additional associated factors have also been identified. However, the components' roles and interactions have not been fully elucidated. The in situ proximity ligation assay (PLA) provides a sensitive means to determine whether proteins and other factors have bound to chromosomes in close proximity to each other, and thus may interact. Thus, we modified, tested, and applied the assay to probe interactions of MSL complex components on polytene chromosomes. We show that in situ PLA can detect and map both protein-protein and protein-ncRNA interactions on polytene chromosomes at high resolution. We further show that all five protein components of the MSL complex are in close proximity to each other, and the ncRNAs roX1 and roX2 bind the complex in close proximity to MLE. Our results also indicate that JIL1, a histone H3 Ser10 kinase enriched on the male X chromosome, interacts with MSL1 and MSL2, but not MSL3 of the MSL complex. In addition, we corroborate proposed interactions of the MSL complex with both CLAMP and TopoII.

Keywords
dosage compensation, protein interaction, polytene chromosomes, MSL-complex
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-100658 (URN)10.1007/s00412-015-0509-x (DOI)000360288200009 ()25694028 (PubMedID)
Funder
Swedish Research Council, 621-2012-2165Swedish Cancer Society, 2011/382
Available from: 2015-03-06 Created: 2015-03-05 Last updated: 2018-06-07Bibliographically approved
Johansson, A.-M. & Larsson, J. (2014). Genome-wide mapping of Painting of fourth on Drosophila melanogaster salivary gland polytene chromosomes. Genomics Data, 2, 63-65
Open this publication in new window or tab >>Genome-wide mapping of Painting of fourth on Drosophila melanogaster salivary gland polytene chromosomes
2014 (English)In: Genomics Data, ISSN 1025-6059, E-ISSN 2213-5960, Vol. 2, p. 63-65Article in journal (Refereed) Published
Abstract [en]

The protein Painting of fourth (POF) in Drosophila melanogaster specifically targets and stimulates expression output from the heterochromatic 4th chromosome, thereby representing an autosome specific protein [1,2]. Despite the high specificity for chromosome 4 genes, POF is occasionally observed binding to the cytological region 2L:31 in males and females [3] and two loci on the X-chromosome, PoX1 and PoX2 only in females [4]. Here we provide a detailed description of the experimental design and analysis of the tiling array data presented by Lundberg and colleagues in G3: Genes, Genomes, Genetics 2013 [4], where the female specific POF binding to PoX1 and PoX2 loci on the X chromosome was reported. We show the genome-wide high resolution binding profile of the POF protein where these different POF binding sites are detected. The complete data set is available at http://www.ncbi.nlm.nih.gov/geo/ (accession: GSE45402).

Keywords
Painting of fourth, Drosophila melanogaster, ChIP-chip
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-112366 (URN)10.1016/j.gdata.2014.04.007 (DOI)26484072 (PubMedID)
Available from: 2015-12-07 Created: 2015-12-07 Last updated: 2018-06-07Bibliographically approved
Figueiredo, M. L. A., Kim, M., Philip, P., Allgardsson, A., Stenberg, P. & Larsson, J. (2014). Non-coding roX RNAs prevent the binding of the MSL-complex to heterochromatic regions. PLoS Genetics, 10(12), e1004865
Open this publication in new window or tab >>Non-coding roX RNAs prevent the binding of the MSL-complex to heterochromatic regions
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2014 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 12, p. e1004865-Article in journal (Refereed) Published
Abstract [en]

Long non-coding RNAs contribute to dosage compensation in both mammals and Drosophila by inducing changes in the chromatin structure of the X-chromosome. In Drosophila melanogaster, roX1 and roX2 are long non-coding RNAs that together with proteins form the male-specific lethal (MSL) complex, which coats the entire male X-chromosome and mediates dosage compensation by increasing its transcriptional output. Studies on polytene chromosomes have demonstrated that when both roX1 and roX2 are absent, the MSL-complex becomes less abundant on the male X-chromosome and is relocated to the chromocenter and the 4thchromosome. Here we address the role of roX RNAs in MSL-complex targeting and the evolution of dosage compensation in Drosophila. We performed ChIP-seq experiments which showed that MSL-complex recruitment to high affinity sites (HAS) on the X-chromosome is independent of roX and that the HAS sequence motif is conserved in D. simulans. Additionally, a complete and enzymatically active MSL-complex is recruited to six specific genes on the 4thchromosome. Interestingly, our sequence analysis showed that in the absence of roX RNAs, the MSL-complex has an affinity for regions enriched in Hoppel transposable elements and repeats in general. We hypothesize that roX mutants reveal the ancient targeting of the MSL-complex and propose that the role of roX RNAs is to prevent the binding of the MSL-complex to heterochromatin.

National Category
Biochemistry and Molecular Biology Genetics Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:umu:diva-93046 (URN)10.1371/journal.pgen.1004865 (DOI)000346649900060 ()25501352 (PubMedID)2-s2.0-84919667251 (Scopus ID)
Funder
Swedish Research Council, 621-2012-2165
Note

Originally included in thesis in manuscript form.

Available from: 2014-09-11 Created: 2014-09-11 Last updated: 2018-06-07Bibliographically approved
Crona, F., Dahlberg, O., Lundberg, L. E., Larsson, J. & Mannervik, M. (2013). Gene regulation by the lysine demethylase KDM4A in Drosophila. Developmental Biology, 737(2), 453-463
Open this publication in new window or tab >>Gene regulation by the lysine demethylase KDM4A in Drosophila
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2013 (English)In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 737, no 2, p. 453-463Article in journal (Refereed) Published
Abstract [en]

Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage. KDM4A demethylates H3K36me3, a modification enriched in the 3' end of active genes. The genomic targets and the role of KDM4 proteins in development remain largely unknown. We therefore generated KDM4A mutant Drosophila, and identified 99 mis-regulated genes in first instar larvae. Around half of these genes were down-regulated and the other half up-regulated in dKDM4A mutants. Although heterochromatin protein 1a (HP1a) can stimulate dKDM4A demethylase activity in vitro, we find that they antagonize each other in control of dKDM4A-regulated genes. Appropriate expression levels for some dKDM4A-regulated genes rely on the demethylase activity of dKDM4A, whereas others do not. Surprisingly, although highly expressed, many demethylase-dependent and independent genes are devoid of H3K36me3 in wild-type as well as in dKDM4A mutant larvae, suggesting that some of the most strongly affected genes in dKDM4A mutant animals are not regulated by H3K36 methylation. By contrast, dKDM4A over-expression results in a global decrease in H3K36me3 levels and male lethality, which might be caused by impaired dosage compensation. Our results show that a modest increase in global H3K36me3 levels is compatible with viability, fertility, and the expression of most genes, whereas decreased H3K36me3 levels are detrimental in males.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
chromatin, histone methylation, gene regulation, Drosophila
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-62070 (URN)10.1016/j.ydbio.2012.11.011 (DOI)000313381200020 ()23195220 (PubMedID)
Available from: 2012-12-13 Created: 2012-12-06 Last updated: 2018-06-08Bibliographically approved
Lundberg, L. E., Stenberg, P. & Larsson, J. (2013). HP1a, Su(var)3-9, SETDB1 and POF stimulate or repress gene expression depending on genomic position, gene length and expression pattern in Drosophila melanogaster. Nucleic Acids Research, 41(8), 4481-4494
Open this publication in new window or tab >>HP1a, Su(var)3-9, SETDB1 and POF stimulate or repress gene expression depending on genomic position, gene length and expression pattern in Drosophila melanogaster
2013 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 41, no 8, p. 4481-4494Article in journal (Refereed) Published
Abstract [en]

Heterochromatin protein 1a (HP1a) is a chromatin-associated protein important for the formation and maintenance of heterochromatin. In Drosophila, the two histone methyltransferases SETDB1 and Su(var)3-9 mediate H3K9 methylation marks that initiates the establishment and spreading of HP1a-enriched chromatin. Although HP1a is generally regarded as a factor that represses gene transcription, several reports have linked HP1a binding to active genes, and in some cases, it has been shown to stimulate transcriptional activity. To clarify the function of HP1a in transcription regulation and its association with Su(var)3-9, SETDB1 and the chromosome 4-specific protein POF, we conducted genome-wide expression studies and combined the results with available binding data in Drosophila melanogaster. The results suggest that HP1a, SETDB1 and Su(var)3-9 repress genes on chromosome 4, where non-ubiquitously expressed genes are preferentially targeted, and stimulate genes in pericentromeric regions. Further, we showed that on chromosome 4, Su(var)3-9, SETDB1 and HP1a target the same genes. In addition, we found that transposons are repressed by HP1a and Su(var)3-9 and that the binding level and expression effects of HP1a are affected by gene length. Our results indicate that genes have adapted to be properly expressed in their local chromatin environment.

Keywords
Drosophila melanogaster, chromatin structure, gene expression, epigenetics
National Category
Genetics
Research subject
Genetics; Molecular Biology
Identifiers
urn:nbn:se:umu:diva-67086 (URN)10.1093/nar/gkt158 (DOI)000318569700019 ()23476027 (PubMedID)
Available from: 2013-03-18 Created: 2013-03-12 Last updated: 2018-06-08Bibliographically approved
Projects
Chromosome-wide regulatory mechanisms in Drosophila [2009-04866_VR]; Umeå UniversityScanFly 2010: 3rd Scandinavian Drosophila Symposium, Vindeln 19-21 May 2010 [2009-07552_VR]; Umeå UniversityChromosome-wide gene regulatory mechanisms [2012-02165_VR]; Umeå UniversityChromosome-wide gene regulatory mechanisms [2016-03306_VR]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-4373-6790

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