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相关概念视频

Pleiotropy01:33

Pleiotropy

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,...
X-Inactivation01:58

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Variants at the Centromere02:30

Histone Variants at the Centromere

Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
X-inactivation01:58

X-inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...

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UTX和JMJD3是参与HOX基因调节和发育的素H3K27脱甲基酶.

Karl Agger1, Paul A C Cloos, Jesper Christensen

  • 1Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.

Nature
|August 24, 2007
PubMed
概括

基因组脱甲基酶UTX和JMJD3可以去除抑制的H3K27me3标记,这对细胞命运和发育至关重要. 它们的活性对于在分化过程中的基因激活和适当的胚胎发育至关重要.

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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.
  • 发育生物学 发展生物学
  • 分子生物学分子生物学

背景情况:

  • 多胞体抑制复合体2 (PRC2) 通过H3K27me3进行转录抑制,这是与干细胞状态相关的表观遗传标记.
  • 在分化过程中,H3K27me3的减少发生,这表明存在特定的基因组脱甲基酶.

研究的目的:

  • 为了识别和表征负责去除H3K27me3标记的基因组脱甲基酶.
  • 研究这些脱甲基酶在发育和分化过程中的基因调节中的作用.

主要方法:

  • 在H3K27me3.3.上测试JmjC域蛋白UTX和JMJD3的脱甲基酶活性的生物化学试验.
  • 在体内实验涉及JMJD3的宫外表达和分析H3K27me3水平和多组蛋白位址.
  • 染色体免疫沉测试以评估UTX与HOXB1位点的结合.
  • 基因操纵 (突变,表达抑制) 的一个 C. elegans JMJD3 正义 (F18E9.5).

主要成果:

  • 确定UTX和JMJD3是人类JmjC域蛋白质,它们去甲基H3K27me3.
  • 宫外JMJD3表达降低了H3K27me3水平,并在体内引起了多组蛋白脱.
  • UTX直接与HOXB1位点结合,并且在分化过程中需要其激活.
  • 抑制C. elegans JMJD3正义基因F18E9.5导致了异常的淋巴腺发育.

结论:

  • 通过UTX/JMJD3蛋白进行H3K27me3脱甲基化对于正常发育和细胞分化至关重要.
  • 这些脱甲基酶在去除抑制表观遗传标记方面发挥着关键作用,促进发育基因的激活.
  • 压制性标记的协调去除和激活标记的沉积对于在分化过程中精确的转录调节至关重要.