类哺乳动物在发育过程中使用各种策略来启动X染色体无活化
Ikuhiro Okamoto1, Catherine Patrat, Dominique Thépot
1Mammalian Developmental Epigenetics Group, Institut Curie, CNRS UMR 3215, INSERM U934, Paris 75248, France.
Nature
|April 8, 2011
概括
雌性哺乳动物利用X染色体失活 (XCI) 来补偿基因剂量. 与小鼠不同,子和人类的XCI发起时间较晚,XIST上调之前的染色体沉默,揭示了哺乳动物的不同发育策略.
科学领域:
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
- 哺乳动物胚胎发生
背景情况:
- 在雌性哺乳动物中,X染色体不活化 (XCI) 均等化X相关基因表达.
- 在小鼠中,父亲的XCI通过XISTRNA被印记,并在内细胞质中逆转,随后在表皮质细胞中随机XCI.
研究的目的:
- 研究和比较子和人类的X染色体失活 (XCI) 启动策略与小鼠的策略.
- 阐明 XIST RNA 印记和上调在不同乳动物早期胚胎生成中的作用.
主要方法:
- 对XIST基因表达和X染色体失活模式的比较分析.
- 在子和人类的胚胎发育研究,专注于囊胚阶段.
- 研究XISTRNA印记及其与XCI定时的相关性.
主要成果:
- 与小鼠相比,子和人类的XCI启动延迟,而XIST不受印记.
- 在子和人类胚胎中,XIST上调发生在X染色体上,甚至在内部细胞质内.
- 在子中,XIST上调可以触发双基XCI,而在人类中,尽管XIST上调,但XCI启动延迟到囊胞阶段之外.
结论:
- 哺乳动物X染色体失活 (XCI) 调节表现出显著的多样性,特别是在早期胚胎发生过程中.
- 启动XCI的时间和机制,包括XIST的作用,在各类eutherian物种之间有很大差异.
- 不活跃的X染色体的选择发生在子和人类的XIST上调的下游,与小鼠模型不同.
相关概念视频
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.
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.
Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...


