This month, Professor Franklin Pugh, Molecular Biology and Genetics, and researchers Chitvan Mittal grad, Olivia Lang grad and William KM Lai grad, discovered that inducible systems work in conjunction with constitutive systems to produce variable outputs in function of the “on” or “off” state of certain cofactors – this highlights new understandings of how the epigenome affects transcription in cells.
The team published their study “An Integrate SAGA and TFID PIC Assembly Pathway Selective For Poised 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 usually activated by environmental changes in the microenvironment. Pugh compared yeast to 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 of humans, so by studying yeast at the molecular level, we get a better understanding of how human genes are regulated at the molecular level.” , Pugh said. “But yeast is not human, so there are also many differences. The fundamentals are quite similar.
With this yeast model, researchers were able to define distinct mechanistic differences between types of inducible versus constitutive systems.
While inducible genes are genes that are only expressed under specific environmental conditions, constitutive genes are genes that are always expressed and serve as the basis for the functioning of gene expression in the genome.
Within the subset of inducible genes are promoters specific to these types of systems that must be engaged or “induced” to effectively activate the gene’s instructions.
The researchers distinguished five pronounced classes of promoters specific to their research goals in their paper: RP, induced, balanced, constitutive, and condition-specific, such as induced by heat shock.
Through complex characterizations of these different types of promoters, researchers have determined a dependency between specific cofactors, or general transcription factors, and inducible promoters.
A cofactor is a molecule attached to a protein that allows it to function. A transcription factor – a protein that takes part in the transcription of DNA into RNA – uses cofactors to transcribe DNA. Transcription is vital for the expression of a protein in a cell, which determines how a cell functions.
The researchers elucidated a dependence of promoters inducible at a high concentration of general transcription factors on a more specific factor associated with TBP – called TBP-associated factors or TAFs.
This dependence suggests a compelling mechanism that could use TAF to create an environment capable of assembling the supplies needed to begin transcribing DNA into RNA, but it warrants further follow-up, the researchers say.
“We would like to try to remove the TAFs by other means [mutations] to achieve that and see if we can get at least a transcript,” Pugh said.
Although this complex communication and receptivity across the yeast and human epigenome can never be fully assessed in a single paper, Pugh points to new directions of research from this new paper with a horizon in rapid evolution.
“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]”, said Pugh. “However, we found one that does: TFIIA. While TFIIA is considered a general transcription factor, it behaves more like a TAF.
Pugh said these findings will provide insight into how small environmental changes can impact our epigenome, opening up new discussions about genetic disorders and other diseases that occur throughout a human’s lifetime.
#Proteomeexpressing #gene #research #shows #reactive #mode #communication #housed #DNA