The fourth chromosome of Drosophila melanogaster has a number of unique properties that make it a convenient model for the study of chromatin structure. Only 4.2 Mb overall, the 1.2 Mb distal arm of ...chromosome 4 seen in polytene chromosomes combines characteristics of heterochromatin and euchromatin. This domain has a repeat density of ~35%, comparable to some pericentric chromosome regions, while maintaining a gene density similar to that of the other euchromatic chromosome arms. Studies of position-effect variegation have revealed that heterochromatic and euchromatic domains are interspersed on chromosome 4, and both cytological and biochemical studies have demonstrated that chromosome 4 is associated with heterochromatic marks, such as heterochromatin protein 1 and histone 3 lysine 9 methylation. Chromosome 4 is also marked by POF (painting-of-fourth), a chromosome 4-specific chromosomal protein, and utilizes a dedicated histone methyltransferase, EGG. Studies of chromosome 4 have helped to shape our understanding of heterochromatin domains and their establishment and maintenance. In this review, we provide a synthesis of the work to date and an outlook to the future.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Recent results from diverse organisms point to a self-reinforcing network of interactions among the three best-characterized covalent modifications that mark heterochromatin: histone hypoacetylation, ...histone H3-Lys9 methylation, and cytosine methylation. These modification systems suggest a mechanistic basis for spreading of heterochromatin over large domains and for stable epigenetic inheritance of the silent state. All three modifications used in packaging heterochromatin are also used in stable silencing of euchromatic genes.
Studies of transcriptional gene silencing in Drosophila melanogaster suggest that most of chromosome 4 resembles pericentric heterochromatin. However, some modifiers of position-effect variegation, ...including chromosome 4 dosage and loss of SU(VAR)3-9, have different effects on silencing in pericentric vs. distal arm chromosome 4 heterochromatin, distinguishing these two heterochromatin types.
The banded portion of Drosophila melanogaster chromosome 4 exhibits euchromatic and heterochromatic characteristics. Reminiscent of heterochromatin, it contains a high percentage of repetitive ...elements, does not undergo recombination, and exhibits high levels of HP1 and histone-3 lysine-9 dimethylation. However, in the distal 1.2 Mb, the gene density is typical of euchromatin, and this region is polytene in salivary gland nuclei. Using P-element reporters carrying a copy of hsp70-white, alternative chromatin packaging domains can be distinguished by the eye color phenotype. Mapping studies identified the repetitive element 1360 as a candidate for heterochromatin targeting in the fourth chromosome Hcf region. We report here two new screens using this reporter to look for additional heterochromatin target sites. We confirm that reporter elements within 10 kb of 1360 are usually packaged as heterochromatin; however, heterochromatin packaging occurs in the sv region in the absence of 1360. Analyses of the sequences adjacent to P-element reporters show no simple association between specific repeated elements and transgene expression phenotype on a whole chromosome level. The data require that heterochromatin formation as a whole depends on a more complex pattern of sequence organization rather than the presence of a single sequence element.
Significant portions of the eukaryotic genome are heterochromatic, made up largely of repetitious sequences and possessing a distinctive chromatin structure associated with gene silencing. New ...insights into the form of packaging, the associated histone modifications, and the associated nonhistone chromosomal proteins of heterochromatin have suggested a mechanism for providing an epigenetic mark that allows this distinctive chromatin structure to be maintained following replication and to spread within a given domain.
In eukaryotes, distinct regions of the genome are packaged as euchromatin (less condensed, more active) or heterochromatin (condensed, silenced). Studies in yeast, plants, and flies suggest that RNA ...interference (RNAi) is linked to heterochromatin formation and transcriptional silencing of transposable element (TE) sequences 1, 2. We previously reported that insertion of a mobile hsp70-white reporter within 10 kb of a 1360 element on chromosome four of Drosophila melanogaster correlates with variegation (silencing) 3. Here, we report small RNAs (∼23 nt) corresponding to 1360, indicating processing by the RNAi machinery. To directly test the ability of 1360 to silence a nearby gene in vivo, we introduced a P element construct carrying a single copy of 1360 upstream of the hsp70-white reporter into flies. This 1360 element contributes to HP1-dependent variegation at a pericentric insertion site, as demonstrated by a decrease in silencing after FLP-mediated removal of 1360. In euchromatin, 1360 is not sufficient to induce silencing, suggesting that proximity to pericentric heterochromatin and/or a high local TE density contributes to heterochromatin formation. Silencing of the 1360, hsp70-white reporter is sensitive to mutations in RNAi components. Our results implicate 1360 as a target for sequence-specific heterochromatic silencing through an RNAi-dependent mechanism.
Although bioinformatics is becoming increasingly central to research in the life sciences, bioinformatics skills and knowledge are not well integrated into undergraduate biology education. This ...curricular gap prevents biology students from harnessing the full potential of their education, limiting their career opportunities and slowing research innovation. To advance the integration of bioinformatics into life sciences education, a framework of core bioinformatics competencies is needed. To that end, we here report the results of a survey of biology faculty in the United States about teaching bioinformatics to undergraduate life scientists. Responses were received from 1,260 faculty representing institutions in all fifty states with a combined capacity to educate hundreds of thousands of students every year. Results indicate strong, widespread agreement that bioinformatics knowledge and skills are critical for undergraduate life scientists as well as considerable agreement about which skills are necessary. Perceptions of the importance of some skills varied with the respondent's degree of training, time since degree earned, and/or the Carnegie Classification of the respondent's institution. To assess which skills are currently being taught, we analyzed syllabi of courses with bioinformatics content submitted by survey respondents. Finally, we used the survey results, the analysis of the syllabi, and our collective research and teaching expertise to develop a set of bioinformatics core competencies for undergraduate biology students. These core competencies are intended to serve as a guide for institutions as they work to integrate bioinformatics into their life sciences curricula.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Analysis of the Neurospora crassa chromodomain protein CDP-2, a component of a newly characterized HP1-containing complex, reveals a second gene-silencing mechanism and provides insights into the ...dynamic nature of chromatin domains that possess shared components.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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