染色体结构因子CTCF对于孕激素依赖的子宫成熟至关重要
Sylvia C Hewitt1, Artiom Gruzdev2, Cynthia J Willson3
1Pregnancy & Female Reproduction, DIR RDBL, NIEHS, Research Triangle Park, North Carolina, USA.
概括
在子宫中CTCF缺失会损害腺体发育,并改变孕激素调节的基因表达,影响子宫平衡和抗瘤发生. 这突显了CTCF在子宫功能中的作用.
科学领域:
- 基因组学和分子生物学
- 生殖生物学 生殖生物学
- 癌症生物学 癌症生物学
背景情况:
- 雌激素和孕受体通过CTCF介导的循环挤出与增强剂相互作用.
- 在人类子宫内膜瘤中,CTCF突变很常见,这表明它在子宫恒温中具有重要作用.
研究的目的:
- 研究CTCF介导的增强剂-基因相互作用对子宫内膜发育和功能的影响.
- 阐明CTCF在子宫对类固醇激素反应中的作用及其对子宫内膜癌的影响.
主要方法:
- 在小鼠雌性生殖组织中选择性删除Ctcf基因 (Ctcfd/d).
- 对子宫组织进行组织学分析,以评估腺体和筋膜发育.
- 转录分析分析基因表达变化.
- 在CTCF删除后对孕激素敏感基因表达的分析.
主要成果:
- 在青春期前的小鼠中,Ctcf的删除导致子宫腺形成减少,并在青春期后的子宫低可塑性.
- 转录分析显示,干细胞标记物 (Lif,EOMES,Lgr5) 和炎症通路的表达增加.
- 切除CTCF影响了对孕激素敏感基因的子集,包括Ihh,Fst和Errfi1,而孕激素信号仍然是功能性的.
结论:
- 子宫CTCF对于最佳的青春期后子宫发育至关重要,它通过调节孕激素依赖的基因表达.
- 依赖CTCF的基因参与了诸如抗瘤发生等关键过程,解释了孕激素在早期子宫内膜瘤中的有效性.
- CTCF在维持子宫平衡和调节对生殖健康至关重要的基因表达方面发挥着至关重要的作用.
相关概念视频
Chromatin Position Affects Gene Expression
23.4K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.4K
Inheritance of Chromatin Structures
6.3K
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...
6.3K
Heterochromatin
14.0K
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...
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...
14.0K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K
Euchromatin
7.0K
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...
7.0K
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K


