Histone H3.3 K27M and K36M mutations de-repress transposable elements through perturbation of antagonistic chromatin marks

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KRAB型锌指蛋白的进化及在物种演化中的功能

C2H2型锌指蛋白家族是目前发现的哺乳动物中最大的转录/转录调控因子家族,由一小群古老的含有真核锌指结构的转录因子经过多次基因复制和功能分化演化而来。KRAB型锌指蛋白(KRAB-containing zinc finger proteins, KRAB-ZFPs)作为C2H2型锌指蛋白家族中最大的亚家族,最早出现在四足脊椎动物,并随物种的进化数量快速增长,在人类中占据C2H2型锌指蛋白的60%左右。在物种演化中,进化压力主要改变KRAB-ZFPs的DNA结合能力,而KRAB-ZFPs介导的转录抑制能力则稳定存在。同时,多种KRAB-ZFPs能够与KRAB相关蛋白1(KRAB-associated protein 1, KAP1)协同作用沉默哺乳动物中反转录元件的活性,并与之协同进化,严格限制反转录原件的跳跃能力。本文综述了KRAB-ZFPs的数量倍增、锌指结构的灵活多变、KRAB-ZFPs/KAP1的转录抑制能力和反转录元件的跳跃性在促进哺乳动物调控网络的差异、基因组稳定性的变化和物种进化中的作用,旨在进一步揭示KRAB-ZFPs在推动物种稳定演化中的特点和功能。     

A Comparison of Internal Eliminated Sequences in the Genes that Encode Two K+-Channel Isoforms in Paramecium tetraurelia

We examined both the somatic (macro-) and the germinal (micronuclear) DNAs that encode two K⁺-channel isoforms. PAK1 and PAK11 , in Paramecium tetraurelia. The coding regions of these two isoforms are 88% identical in nucleotides and 95% identical in amino acids. Their introns are also highly conserved. Even some of the internal eliminated sequences in PAK1 and PAK11 are clearly related. PAK1 has five IESs; PAK11 has four. The first (5'-most) IESs of the two genes are located at the same site in the coding sequence but differ in size. The 2nd IES in PAK1 (206-bp), the largest among the nine IESs, has no PAK11 counterpart. The 3rd, 4th and 5th IESs in PAK1 have a counterpart in PAK11 that is similar in size and in sequence, and identical in its position in the coding sequence. In addition, the first IES of PAK11 bears some resemblance to the 4th one of PAK1. The similarities and differences between the two sets of IESs are discussed with respect to the origin and divergence of the two K⁺-channel isoforms.     

P53 and the defenses against genome instability caused by transposons and repetitive elements

The recent publication by Wylie et al. is reviewed, demonstrating that the p53 protein regulates the movement of transposons. While this work presents genetic evidence for a piRNA‐mediated p53 interaction with transposons in Drosophila and zebrafish, it is herein placed in the context of a decade or so of additional work that demonstrated a role for p53 in regulating transposons and other repetitive elements. The line of thought in those studies began with the observation that transposons damage DNA and p53 regulates DNA damage. The presence of transposon movement can increase the rate of evolution in the germ line and alter genes involved in signal transduction pathways. Transposition can also play an important role in cancers where the p53 gene function is often mutated. This is particularly interesting as recent work has shown that de‐repression of repetitive elements in cancer has important consequences for the immune system and tumor microenvironment.     

Assembly of the <Emphasis Type="Italic">Tc1</Emphasis> and <Emphasis Type="Italic">mariner</Emphasis> transposition initiation complexes depends on the origins of their transposase DNA binding domains

In this review, we focus on the assembly of DNA/protein complexes that trigger transposition in eukaryotic members of the IS630–Tc1–mariner (ITm) super-family, the Tc1- and mariner-like elements (TLEs and MLEs). Elements belonging to this super-family encode transposases with DNA binding domains of different origins, and recent data indicate that the chimerization of functional domains has been an important evolutionary aspect in the generation of new transposons within the ITm super-family. These data also reveal that the inverted terminal repeats (ITRs) at the ends of transposons contain three kinds of motif within their sequences. The first two are well known and correspond to the cleavage site on the outer ITR extremities, and the transposase DNA binding site. The organization of ITRs and of the transposase DNA binding domains implies that differing pathways are used by MLEs and TLEs to regulate transposition initiation. These differences imply that the ways ITRs are recognized also differ leading to the formation of differently organized synaptic complexes. The third kind of motif is the transposition enhancers, which have been found in almost all the functional MLEs and TLEs analyzed to date. Finally, in vitro and in vivo assays of various elements all suggest that the transposition initiation complex is not formed randomly, but involves a mechanism of oriented transposon scanning. Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at . An erratum to this article can be found at     

Vege and Mar: two novel hAT MITE families from Drosophila willistoni

Two novel families of miniature inverted repeat transposable elements (MITEs), Vege and Mar, are described from Drosophila willistoni. Based on their structures, both element families are hypothesized to belong to the hAT superfamily of transposable elements. Both elements have perfect, inverted terminal repeats and 8-bp target site duplications and were found to have inserted within fixed copies of nonautonomous P elements. Vege is present in all studied D. willistoni populations and appears to have a relatively low copy number. Mar was identified in only a single D. willistoni population, and its copy number is presently unknown. Although MITEs occupy relatively large proportions of the genomes of a broad range of organisms, this may be their first unambiguous identification in any species of the genus Drosophila.     

Nucleotide sequence of the transposable element IS15

We have determined the complete nucleotide sequence of the right (R) copy of the insertion sequence IS15 which flanks, in direct orientation, the composite transposon Tn1525. IS15-R, which is capable of independent transposition, is 1648 bp long and has short (14 bp) perfect inverted repeats at its termini. Analysis of the nucleotide sequence indicates that IS15-R results from the transposition, in direct orientation, of a smaller (820 bp long) IS, designated IS15-Δ, into itself. This integration event is accompanied by the duplication of 8 bp in the target DNA. IS15-Δ possesses two large overlapping open reading frames (ORF) located on opposite strands. Because of this particular structure, IS15 possesses four large ORFs which, due to the integration event, exhibit some differences with those of the parental 1S15-Δ.     

Location of ribosome-binding sites in the nin5 region of bacteriophage lambda

Seven ribosome-binding sites on DNA have been located within the region defined by the nin5 deletion as well as several ribosome-binding sites on each side of the nin5 region. These were mapped by electron microscopy relative to the end points of the nin5 deletion and two Tn903 transposons, one inserted into gene Rz and another inserted near gene Q. These ribosomes binding sites within the nin5 region may correspond to polypeptide initiation sites for up to seven new dispensible lambda genes.