Epigenetic Silencing of P-Element Reporter Genes Induced by Transcriptionally Active Domains of Constitutive Heterochromatin in Drosophila melanogaster.
Epigenetic Silencing of P-Element Reporter Genes Induced by Transcriptionally Active Domains of Constitutive Heterochromatin in Drosophila melanogaster.
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DOI：
10.3390/genes14010012
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发表时间：
2022-12-21
期刊：
影响因子：
3.5
通讯作者：
Dimitri, Patrizio
中科院分区：
文献类型：
--
作者：
Messina, Giovanni;Celauro, Emanuele;Marsano, Rene Massimiliano;Prozzillo, Yuri;Dimitri, Patrizio
关键词：
通过P元件整合到果蝇基因组不同位置的报告基因通常被用来监测染色质结构域的功能状态。通常认为，P元件衍生的报告基因在转座到结构性异染色质时会受到位置效应变异(PEV)的影响，因为它们获得了促进沉默的异染色质样表观遗传修饰。然而，对黑腹果蝇基因组的测序和注释表明，构成异染色质是一个遗传和分子上的异质性隔室。事实上，除了重复的DNA外，它还包含数百个功能基因，加在一起占其整个基因组领土的很大一部分。值得注意的是，这些基因中的大多数在不同的发育阶段和组织中都活跃地转录，无论它们在异染色质中的位置如何。在黑腹果蝇PEV的遗传学和分子研究中，一个悬而未决的问题是，功能异染色质结构域，即含有活性基因的异染色质结构域，是否能够沉默转座的报告基因，或者相反，是否能够驱动它们的表达。在这项工作中，我们提供的实验证据表明，即使当PW+报告基因整合在2号染色体着丝粒周围区域的活跃转录区域内或附近时，也会诱导PW+报告基因的强烈沉默。有趣的是，一些PW+报告基因被发现对已知的PEV抑制子的作用不敏感。其中两个基因被插入到Yeti基因中，Yeti基因表达在2号染色体的深层异染色质中，带有活性染色质标记。对抑制子展示的PW+记者的不同敏感性支持这样的观点，即不同的表观遗传调节因子或机制控制着异染色质的不同区域。总之，我们的结果表明，关于PEV背后的分子机制可能有更多的复杂性。
Reporter genes inserted via P-element integration into different locations of the Drosophila melanogaster genome have been routinely used to monitor the functional state of chromatin domains. It is commonly thought that P-element-derived reporter genes are subjected to position effect variegation (PEV) when transposed into constitutive heterochromatin because they acquire heterochromatin-like epigenetic modifications that promote silencing. However, sequencing and annotation of the D. melanogaster genome have shown that constitutive heterochromatin is a genetically and molecularly heterogeneous compartment. In fact, in addition to repetitive DNAs, it harbors hundreds of functional genes, together accounting for a significant fraction of its entire genomic territory. Notably, most of these genes are actively transcribed in different developmental stages and tissues, irrespective of their location in heterochromatin. An open question in the genetic and molecular studies on PEV in D. melanogaster is whether functional heterochromatin domains, i.e., heterochromatin harboring active genes, are able to silence reporter genes therein transposed or, on the contrary, can drive their expression. In this work, we provide experimental evidence showing that strong silencing of the Pw+ reporters is induced even when they are integrated within or near actively transcribed loci in the pericentric regions of chromosome 2. Interestingly, some Pw+ reporters were found insensitive to the action of a known PEV suppressor. Two of them are inserted within Yeti, a gene expressed in the deep heterochromatin of chromosome 2 which carries active chromatin marks. The difference sensitivity to suppressors-exhibited Pw+ reporters supports the view that different epigenetic regulators or mechanisms control different regions of heterochromatin. Together, our results suggest that there may be more complexity regarding the molecular mechanisms underlying PEV.
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影响因子：
1.7
作者：
Dimitri, P;Bucheton, A
通讯作者：
Bucheton, A
DOI：
10.1098/rstb.1986.0004
发表时间：
1986-01-29
影响因子：
6.3
作者：
FLAVELL, RB
通讯作者：
FLAVELL, RB
影响因子：
1.6
作者：
Corradini, N;Rossi, F;Dimitri, P
通讯作者：
Dimitri, P
影响因子：
3.3
作者：
Haynes, Karmella A.;Gracheva, Elena;Elgin, Sarah C. R.
通讯作者：
Elgin, Sarah C. R.
影响因子：
56.9
作者：
COOLEY, L;KELLEY, R;SPRADLING, A
通讯作者：
SPRADLING, A