ASH2L通过H3K4me3修饰调解表皮分化和毛囊形态发生
Qirui Wang1, Siyi Zeng1, Yimin Liang1
1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
The Journal of investigative dermatology
|April 6, 2024
概括
ASH2L是COMPASS的关键组成部分,对小鼠的表皮发育和毛囊形成至关重要. 它的删除会损害表皮分化,并通过调节特定的基因表达来延迟毛囊形态发生.
科学领域:
- 表观遗传学和发育生物学
- 哺乳动物的表皮发育.
- 基质子的修改 基质子的修改
背景情况:
- 外皮发育涉及复杂的分子调节,包括基质子修饰.
- 由COMPASS进行的Histon H3 lysine K4甲基化 (H3K4me3) 与基因激活有关,但其在表皮系系中的作用尚不清楚.
- ASH2L 是 COMPASS 甲基转移酶复合物的核心子单元.
研究的目的:
- 调查ASH2L在小鼠表皮系发育过程中的表皮原生细胞中的作用.
- 在ASH2L删除的背景下,识别由H3K4me3调节的下游目标基因.
主要方法:
- 在表皮原生细胞中构建具有特定ASH2L缺失的小鼠模型.
- 对新生儿和晚期小鼠表皮和毛囊发育表型的分析.
- 结合RNA测序与Cleave Under Targets和标记 (CUT&Tag) 测序,以识别H3K4me3目标基因.
主要成果:
- 删除ASH2L导致表皮薄化和发形态发生延迟.
- 观察到表皮和毛囊前代细胞的增殖能力下降.
- 在后来的发育阶段,表皮干细胞池的潜在耗尽.
- 确定了下游目标,包括发毛囊发育的基因 (Shh,Edar,Fzd6),Notch信号 (Notch2,Notch3,Hes5,Nrarp) 和 ΔNp63.3.
结论:
- ASH2L依赖的H3K4me3修饰是一种重要的上游表观遗传调节器.
- 这种表观遗传调节对于哺乳动物表皮分化和毛囊形态生成至关重要.
- ASH2L在维持表皮和毛囊前代细胞增殖和干细胞池方面发挥着至关重要的作用.
相关概念视频
01:06Multipotency and Niche of Bulge Stem Cell
3.6K
A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
3.6K
01:12Renewal of Skin Epidermal Stem Cells
2.5K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.5K
02:33Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
03:17Inheritance of Chromatin Structures
6.2K
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...
6.2K
02:32Histone Modification
13.3K
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...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
02:25Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K