This month, Franklin Pugh Professor of Molecular Biology and Genetics, and researchers Chitvan Mittal grad, Olivia Lang grad, and William KM Lai grad, discovered that inducible systems work in tandem with constitutive systems to produce state-variable results.” on” or “on”. “Off” state of certain cofactors: This highlights new insights into how the epigenome affects transcription within cells.
The team posted their to study “A selective SAGA and TFID PIC integrated assembly pathway for equilibrated and induced promoters” in the journal Genes and Development.
The study used yeast as a model to determine the functionality of inducible systems within the genome dedicated to gene expression. Inducible systems are systems that are normally activated by environmental changes in the microenvironment. Pugh compared yeast as a simpler model to study the molecular machinery that regulates genes in humans.
“It turns out that the molecular machinery that regulates genes in yeast is quite similar to that in humans, so by studying yeast at the molecular level, we gain a better understanding of human gene regulation at the molecular level,” he said. pugh. “But yeast is not human, so there are also many differences. The fundamentals are quite similar.”
With this yeast model, the researchers were able to define distinct mechanistic differences between types of inducible systems compared to constitutive systems.
While inducible genes are genes that are only expressed under specific environmental conditions, housekeeping genes are genes that are always expressed and serve as the basis for the functioning of gene expression in the genome.
Within the subgroup of inducible genes there are promoters specific to this type of system that have to be activated or “induced” to effectively activate the instructions of the gene.
The researchers distinguished five pronounced classes of promoters specific to their research goals in their paper: RP, induced, equilibrated, constitutive, and condition-specific, such as being induced by heat shock.
Through complex characterizations of these different types of promoters, the researchers determined a dependency between specific cofactors, or general transcription factors, and inducible promoters.
A cofactor it is a molecule attached to a protein that allows it to function. A transcription factor, a protein involved in the transcription of DNA into RNA, uses cofactors to transcribe DNA. Transcription is vital to the expression of a protein in a cell, which determines how a cell functions.
The researchers elucidated a dependence of inducible promoters on a high concentration of general transcription factors to a more specific TBP-associated factor, called TBP-associated factors or TAF.
This dependency suggests a compelling mechanism that TAF could absorb to create an environment capable of assembling the supplies needed to start transcribing DNA into RNA, but this warrants further follow-up, the researchers say.
“We would like to try to eliminate the TAF in other ways [mutations] to accomplish this and see if we can get at least some transcript,” Pugh said.
Although this complex communication and responsiveness throughout the yeast and human epigenome can never be fully assessed in a single paper, Pugh points to new research directions from this new paper with a rapidly changing horizon.
“What we found is that most PICs [pre-initiation complex] components such as TFIIB, TBP [and] RNA polymerase II does not [contact or interact with specific transcription factors]Pugh said. “However, we found one that does: TFIIA. While TFIIA is thought to be a general transcription factor, it behaves more like a TAF.”
Pugh said these findings will improve our understanding of how small environmental changes can affect our epigenome, opening up further discussions about genetic disorders and other diseases that arise throughout a human’s lifetime.