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相关概念视频

DNA-only Transposons02:57

DNA-only Transposons

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DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
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Overview of Transposition and Recombination02:13

Overview of Transposition and Recombination

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Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
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LTR Retrotransposons03:08

LTR Retrotransposons

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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
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Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

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Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
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Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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RNA Polymerase II Accessory Proteins02:36

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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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在染色体外DNA中从可转移元素中激活增强剂.

Katerina Kraft1, Sedona E Murphy2,3,4, Matthew G Jones1

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bioRxiv : the preprint server for biology
|September 16, 2024
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概括

结直肠癌中的外染色体DNA (ecDNA) 可以激活通常静默的重复元素,驱动MYC瘤基因放大和瘤进化. 对ecDNA的这种重新激活为癌症诊断和治疗提供了新的途径.

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科学领域:

  • 癌症生物学 癌症生物学
  • 基因组学就是基因组学.
  • 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

  • 外染色体DNA (ecDNA) 在侵袭性癌症中普遍存在,促进瘤基因放大和瘤异质性.
  • 对于ecDNA的核组织和监管潜力,人们对其的理解尚不完全.

研究的目的:

  • 在结直肠癌中研究MYC增强的ecDNA的核架构.
  • 识别和描述与ecDNA相互作用的重复元素,并探索它们的调节作用.

主要方法:

  • 利用Hi-C,超分辨率成像和长读测序来分析结直肠癌细胞中的ecDNA.
  • 专注于一个特定的LINE/L1重复元素,与MYC在ecDNA上共同放大.

主要成果:

  • 在ecDNA和68个重复元素 (ecDNA相互作用元素或EIEs) 之间观察到频繁的空间接近.
  • 一个特定的L1M4a1#LINE/L1 EIE,通常沉默,获得增强器标记,并与MYC在ecDNA上共同放大.
  • 这种EIE增强了MYC表达,对癌细胞存活至关重要,作为MYC上游的结构变体.

结论:

  • 沉默的重复基因组元素可以在ecDNA上被重新激活和功能合作.
  • 在ecDNA上重复元素的激活有助于加速瘤的进化和异质性.
  • 这些发现表明潜在的诊断和治疗策略针对ecDNA介导的重复激活.