Examining the dynamic and regulatory pattern of the mitotic bookmark

Dynamics of transcription factor enrichment during mitosis.ONE) Heatmap showing the enrichment score of 241 TFs along the pseudotime trajectory. The color bar on the left of the heat map showed the Pearson correlation coefficient (p) between the TF enrichment score and pseudotime. (si) Bubble plots showing the dynamics of TF occupancy in chromatin along the pseudo-time trajectory. The position of each bubble along its X The axis indicated the pseudotime at which the TF reached its maximum enrichment score, which was defined as the TF enrichment time. The size of the bubble represented the mean enrichment score of that TF in the pseudo-time trajectory. The color bar at the bottom indicated the proportion of each drug-treated group in the window, chromatin accessibility, and enrichment time along the track. (do) Scatter plot showing the Pearson correlation between TF enrichment time and the ratio of bookmarked regions to TF target regions. Each dot represented a mitotically enriched TF, and TF target regions were defined as the open regions containing the TF motif. Credit: Advances in Science (2023). DOI: 10.1126/sciadv.add2175

Recently, a team led by Prof. Qu Kun from the University of Science and Technology (USTC) of the Chinese Academy of Sciences (CAS) in collaboration with a team led by Prof. Wang Zhikai from the Hefei National Laboratory of Natural Sciences in The Microscale (HFNL) revealed a dynamic and regulatory map of chromatin accessibility that reveals important bookmarking factors. The result was published on Advances in Science.

Mitosis is accompanied by histone changes, loss of chromatin accessibility and silencing of gene transcription. However, there are emerging observations showing that some chromatin features are partially or fully maintained during mitosis, conveying gene regulatory architectures such as “bookmarks”, known as “mitotic bookmarking”.

The structural and functional states of active genes could be marked to ensure their correct reactivation after mitosis, which is necessary for the transmission of transcriptional memory from mother cells to daughter progeny.

In the study, the researchers used the plate-based transposase-accessible chromatin sequencing (scATAC-seq) technique to analyze 6538 mitotic cells and characterize the dynamics of chromatin accessibility during mitosis. Using pseudo-temporal inference analysis, they obtained a two-dimensional map of the cells’ chromatin accessibility and found that chromatin accessibility continued to decrease after mitotic entry and then began to increase at the metaphase-anaphase transition.

Based on the map, they found a subset of chromatin regions that remained open throughout mitosis and termed these “bookmarked regions.” These regions were enriched in gene promoters that were rapidly reactivated after mitosis.

As open chromatin is often occupied by transcription factors (TFs), researchers investigated which TFs exert potential regulatory functions after metaphase. Using TF binding motif enrichment analysis, they found the CCAAT motif of nuclear transcription factor Y subunit α(NF-YA) to be the most enriched motif in these regions.

They further showed that NF-YA functioned as a bookmark TF by preferentially occupying bookmark regions, and NF-YA knockdown (KD) reduced the expansion of chromatin accessibility and transcriptional reactivation during mitotic exit. They confirmed the bookmarking role of NF-YA by performing a depletion experiment, the result of which is consistent with the conclusion.

More information:
Qiaoni Yu et al, Dynamics and regulation of mitotic chromatin bookmark accessibility in single-cell resolution, Advances in Science (2023). DOI: 10.1126/sciadv.add2175

Provided by the University of Science and Technology of China

Reference: Examining the dynamic and regulatory blueprint of mitotic bookmarking (2023, March 15) Retrieved March 15, 2023, from https://phys.org/news/2023-03-dynamic-regulatory-blueprint-mitotic-bookmarking.html

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