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相关概念视频

Pleiotropy01:33

Pleiotropy

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Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Regulation of Expression Occurs at Multiple Steps02:24

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Combinatorial Gene Control02:33

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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Master Transcription Regulators02:23

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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一个AUTS2-Polycomb复合体激活了中枢神经系统中的基因表达.

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自闭症易感候选人2 (AUTS2) 惊人地与Polycomb抑制综合体1 (PRC1) 合作,激活,而不是抑制基因转录. 这一发现将表观遗传调节与神经发育和疾病联系起来.

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科学领域:

  • 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
  • 神经生物学 神经生物学 神经生物学
  • 分子生物学分子生物学

背景情况:

  • 众所周知,多镇压复合体1 (PRC1) 具有基因抑制作用.
  • 自闭症易感候选人2 (AUTS2) 与神经元疾病有关,但其机制尚不清楚.
  • AUTS2 在自然发生的PRC1.1变异中被发现.

研究的目的:

  • 研究PRC1复合体 (PRC1-AUTS2) 中的AUTS2在神经发育中的作用.
  • 阐明PRC1-AUTS2影响基因转录的机制.

主要方法:

  • 生物化学研究分析PRC1-AUTS2复合物的活性.
  • 染色体免疫沉,然后进行测序 (ChIP-seq) 来识别AUTS2基因组标.
  • 在小鼠模型中对Auts2的条件向.

主要成果:

  • PRC1-AUTS2复合体激活了转录,与规范的PRC1功能相反.
  • CK2中和了PRC1的抑制活动,而AUTS2则招募了P300来激活基因.
  • AUTS2通过促进体协会调节神经元基因表达.
  • 在小鼠中枢神经系统中,有条件的Auts2删除会导致发育缺陷.

结论:

  • AUTS2 颠覆了 PRC1 的活动,将其从抑制转变为激活.
  • 这种机制将PRC1-AUTS2的表观遗传调节与神经元基因表达和发育联系起来.
  • 这些发现为与AUTS2中断相关的神经元疾病的发病提供了洞察力.