Harvard Assistant Prof. Alexander Gimelbrant on epigenetic regulation, olfactory receptors, and inheritance of cell state
How can genetically equal cells can play different role in organisms? Why chromosome incativation is needed but may lead to deseases? Harvard Medical School Assistant Professor Alexander Gimelbrant talks on unexpected ways of gene expression regulation.
We’re starting as one cell, as a zygote and then some cells know that they’re liver cells and some cells know that they’re brain cells, some cells know that they’re lymphocytes and so forth and they remember their state. Then some whatever outlier cell has gone crazy and is becoming a cancer. So again this is a state, so genomically they could be absolutely identical but they have very, very different programs running through them and they have different memories of what their identity is.
An extra copy of a single chromosome can lead to very drastic states. For example, Down syndrome is an extra copy of chromosome 21, is trisomy 21. So having basically an extra copy of an X chromosome which is much larger than chromosome 21 could be pretty dangerous. So what happens in fact that women just like man have essentially one active copy because one copy is turned off. Sometime early in the development what happens is that both X chromosomes are active at some point and then a decision is made as this early pluripotent cells dividing, differentiating, become specific tissues, the cells make a decision. So one cell says ‘Okay, I will turn off a paternal X chromosome’ and then all its progeny, every cell that results from it remembers that decision and the same chromosome is off everywhere. And another cell decides ‘Oh, I will turn off maternal chromosome’ and again this decision is very stable over any number of cell divisions and propagates.
So the long story short, the answer is that 10 to 15 percent of genes are showing that type of regulation in a given cell type. Actually almost any reasonable question is open right now because it’s something that is completely new, people haven’t expected this to happen. So we don’t know what the mechanisms are, we don’t even fully know if it’s one mechanism for all of these hundreds or thousands of genes, we don’t know when that happens in the development. So we know when X inactivation happens, we don’t know when this happens. We don’t know what is the real function for this. And then finally we don’t know how to manipulate this.