Saakshi Bangera, DY Patil School of Biotechnology and Bioinformatics
Hair cells in the inner ear and Merkel cells of the skin have distinct similarities in their development. These hair cells specialize in capturing sound vibrations in the inner part of the ear, whereas Merkel cells of the epidermis can sense a touch at the surface of the skin. Despite having varied functions, both of these cells have marked similarities. This study suggests that this resemblance is likely due to a shared evolutionary history between hair cells and Merkel cells. The study also demonstrates that this similarity also exists at an epigenetic level.
The study
Haoze Yu – a PhD student, and Litao Tao – a postdoctoral researcher along with their colleagues, studied this similarity. They pinpointed the shared mechanism of gene regulation that allows the progenitor cells and the stem cells to differentiate into specialized ones.
During embryonic development, transcription factors control the steps in the differentiation. The cascades of transcription factors cooperate with chromatin structures that are specific to a certain lineage. Atonal homolog 1 (ATOH1) – a principal regulator of transcription, is necessary for the differentiation of hair cells of the inner ear and Merkel cells of the epidermis. This study shows that ATOH-1 ceases to access the chromatin of progenitor cells due to the tight configuration of DNA. This eventually ceases the differentiation of both the mechanoreceptor cell types.
The feed-forward mechanism of ATOH1 helps overcome this block. ATOH1 stimulates the production of a protein called POU class 4 transcription factor 3 (POU4F3) – a pioneer factor. This pioneer factor accesses the blocked ATOH1 enhancers by binding to the inaccessible chromatin of progenitor cells. After having bound itself to the closed chromatin, the ATOH1 starts allowing for the differentiation of the progenitors into hair cells and Merkel cells.
The study also demonstrates that specific regions of chromatin in POU4F3 and ATOH1 overlap each other. Due to this overlapping, ATOH1 and POU4F3 share enhancer networks in Merkel cells and hair cells.
Significance and summary
Embryonic growth depends on the transcription factor expression and the changes in the chromatin structure. However, the mechanisms controlling this are less researched. Thus, the study demonstrates a feed-forward mechanism involving ATOH1 – a transcription factor that regulates differentiation, and POU4F3. The study also demonstrates that the protein POU4F3 makes it possible for ATOH1 to access its enhancer complex in close chromatin. This access overcomes the blocking and allows differentiation of progenitor cells into Merkel cells and hair cells. These cells derive from a common cuticular origin and share a deep lineage relationship. Both of these cell types stem from distinct parts of the embryo and nevertheless sense mechanical stimuli. The study suggests that this mechanism had appeared before the hair cells and Merkel cells separated from a common ancestor.
Also read: Brain networks control neural activity and communication
Source:
- Yu, H. V., Tao, L., Llamas, J., Wang, X., Nguyen, J. D., Trecek, T., & Segil, N. (2021). POU4F3 pioneer activity enables ATOH1 to drive diverse mechanoreceptor differentiation through a feed-forward epigenetic mechanism. Proceedings of the National Academy of Sciences, 118(29), e2105137118. https://doi.org/10.1073/pnas.2105137118
- A common ancestor for cells involved in hearing and touch. (n.d.). ScienceDaily. Retrieved July 21, 2021, from https://www.sciencedaily.com/releases/2021/07/210712150320.htm
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About the author: Saakshi is currently pursuing MSc in Biotechnology from DY Patil School of Biotechnology and Bioinformatics. She believes that she doesn’t have a specific area of interest yet. She wishes to explore toxicology and food biotechnology. She’s quite passionate about Biotechnology and aims to grab every opportunity she comes across.
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