Amazing stuff! From pluripotency to totipotency! This is possibly a breakthrough!
"... When an embryo consists of two cells, these cells possess a property called totipotency, or the ability for all things. These cells are capable of transforming into not only all body tissue types but also placenta. Once the embryo reaches the four-cell stage, some of its cells start losing their totipotency and subsequently became pluripotent, or possessing the ability for many things – that is, they can give rise to any type of body tissue, but not to that of the placenta. ...
Now, Weizmann researchers have found a novel way to take this reprogramming even further – namely, returning pluripotent embryonic stem cells to a totipotent, two-cell state. The scientists accomplished this feat by manipulating a new kind of mechanism they discovered: a change in the shape of DNA’s chromatin packaging ...
Now, Weizmann researchers have found a novel way to take this reprogramming even further – namely, returning pluripotent embryonic stem cells to a totipotent, two-cell state. The scientists accomplished this feat by manipulating a new kind of mechanism they discovered: a change in the shape of DNA’s chromatin packaging ...
One of its protein components, called histone H1, is tagged by a protein belonging to a family of small ubiquitin-like modifiers, or SUMO. Instead of marking proteins for degradation, like ubiquitin, its famous cousin, SUMO modifies their function. ...
When the scientists genetically manipulated embryonic stem cells to remove histone H1 proteins or the enzyme responsible for SUMO tagging, these cells reverted to totipotency, regaining their ability to form placental tissue. Not only did their chromatin open up, but more than a hundred genes involved in totipotency were once again expressed. ..."From the abstract:
"The fidelity of the early embryonic program is underlined by tight regulation of the chromatin. Yet, how the chromatin is organized to prohibit the reversal of the developmental program remains unclear. Specifically, the totipotency-to-pluripotency transition marks one of the most dramatic events to the chromatin, and yet, the nature of histone alterations underlying this process is incompletely characterized. Here, we show that linker histone H1 is post-translationally modulated by SUMO2/3, which facilitates its fixation onto ultra-condensed heterochromatin in embryonic stem cells (ESCs). Upon SUMOylation depletion, the chromatin becomes de-compacted and H1 is evicted, leading to totipotency reactivation. Furthermore, we show that H1 and SUMO2/3 jointly mediate the repression of totipotent elements. Lastly, we demonstrate that preventing SUMOylation on H1 abrogates its ability to repress the totipotency program in ESCs. Collectively, our findings unravel a critical role for SUMOylation of H1 in facilitating chromatin repression and desolation of the totipotent identity."
SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity (no public access)
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