Study furthers radically new view of gene control

Study furthers radically new view of gene control

Publication date: Aug 09, 2019

Credit: CC0 Public Domain In recent years, MIT scientists have developed a new model for how key genes are controlled that suggests the cellular machinery that transcribes DNA into RNA forms specialized droplets called condensates.

These droplets occur only at certain sites on the genome, helping to determine which genes are expressed in different types of cells.

In a new study that supports that model, researchers at MIT and the Whitehead Institute for Biomedical Research have discovered physical interactions between proteins and with DNA that help explain why these droplets, which stimulate the transcription of nearby genes, tend to cluster along specific stretches of DNA known as super enhancers.

“This study provides a fundamentally important new approach to deciphering how the ‘dark matter’ in our genome functions in gene control,” says Richard Young, an MIT professor of biology and member of the Whitehead Institute.

Previous research has shown that many of these genes are located near super enhancers, which bind to proteins called transcription factors that stimulate the copying of nearby genes into RNA.

In a 2017 Cell paper, based on computational studies, they hypothesized that in these regions, transcription factors form droplets called phase-separated condensates.

Made of clusters of transcription factors and other molecules, these droplets attract enzymes such as RNA polymerases that are needed to copy DNA into messenger RNA, keeping gene transcription active at specific sites.

As one possible explanation for that site specificity, the research team hypothesized that weak interactions between intrinsically disordered regions of transcription factors and other transcriptional molecules, along with specific interactions between transcription factors and particular DNA elements, might determine whether a condensate forms at a particular stretch of DNA.

In this study, computational modeling and experimentation revealed that the cumulative force of these weak interactions conspire together with transcription factor-DNA interactions to determine whether a condensate of transcription factors will form at a particular site on the genome.

Concepts Keywords
ALS Branches of biology
Amyotrophic Lateral Sclerosis Gene expression
Biochemical Biochemistry
Cancer Enhancer
CC0 Super-enhancer
Chemical Engineering Transcription factor
Chemistry Protein complex
Computational Modeling DNA
Condensate ENCODE
Condensates Cellular machinery
Cooperative Droplets oil
Cytoplasm Transcription machinery
Dark Matter Biological systems
Dewpoint
DNA
Enhancer
Enhancers
Evolution
Fair Dealing
Force
Fruit Fly
Gene
Genome
Harvard
Huntington
Interact
Intrinsically Disordered Regions
Krishna
Lock
Locus
Membrane
Messenger RNA
MGH
MIT
Mit
Neurodegenerative Disorders
Neurons
Oil
Phillip Sharp
Regulatory Regions
RNA
Sabari
Salad Dressing
Transcription
Transcription Factor
Transcription Factors
Weak Interactions
Whitehead Institute

Semantics

Type Source Name
gene UNIPROT IGFALS
disease DOID amyotrophic lateral sclerosis
disease MESH amyotrophic lateral sclerosis
disease MESH neurodegenerative disorders
gene UNIPROT LARGE1
gene UNIPROT KCNK3
gene UNIPROT REST
gene UNIPROT SPEN
disease MESH Cancer
disease DOID Cancer
disease MESH separated

Similar

Leave a Comment

Your email address will not be published. Required fields are marked *