Chromatin organization and gene regulation

Making sense of genetic switches

As part of President Obama’s Precision Medicine Initiative, researchers will gather genomic, transcriptomic and other data from a cohort of a million volunteers. Will we have the ability to interpret the enormous amount of information that will emerge from this effort? In particular, will we be able to define the significance of differences that occur between individuals and that could predispose a person to one of many diseases that contain a genetic component? The answers will depend in large part on our understanding of the mechanisms of gene regulation.  

In the time since Jacob and Monod first proposed the concept of transcriptional regulators and cis-regulatory sequences 55 years ago, the field of gene regulation has undergone a series of important developments. Among these are an ever greater understanding of the enzymes and proteins that shape chromatin architecture and the realization that three-dimensional chromatin architecture is involved intimately in gene regulation. The development of high-throughput technologies for defining chromatin structure and organization, the identification of potential cis-regulatory sequences at a genomic level, and the discovery of roles for noncoding RNAs in chromatin remodeling and gene regulation have facilitated this paradigm shift. Our symposium for the 2016 American Society for Biochemistry and Molecular Biology annual meeting will make sense of these developments and consider the intimate links between transcription regulation, genomic stability and human disease.

Chromatin organization

How are chromosomes organized in the nucleus? How does chromatin organization affect gene regulation in eukaryotes? With the rapid advances in sequencing-based technologies for mapping chromatin organization, the answers to these questions are emerging and will be addressed in the first session.

Transcriptional regulatory mechanisms

Many transcription regulators have been identified over the past two decades. But much remains to be learned about the molecular mechanisms by which they work together to control transcriptional output during normal development and cellular function and during disease states. Presentations in this session will highlight how mutations in components of the basic transcription machinery give rise to developmental disorders and cancer. Also addressed will be our increasing appreciation of the crosstalk between transcriptional regulation and DNA repair processes.

Chromatin remodeling and epigenetics

The third session will focus on mechanisms of epigenetic regulation. DNA methylation is a well-established epigenetic mark with important roles in gene regulation. Emerging evidence that methylation of mRNAs and other transcripts also can have a substantial impact on regulatory processes will be discussed. Understanding mechanisms responsible for epigenetic regulation via chromatin requires a detailed knowledge of histone chaperones and chromatin remodeling enzymes, and these also will be a focus of this session.

Noncoding RNA and gene regulation

With most of the human genome transcribed into RNA during at least some stage of development, a major challenge is to understand the biological functions, where they exist, of the plethora of newly identified noncoding RNA transcripts. A variety of such RNA transcripts have been characterized and linked to gene regulation, and these will be featured in the fourth session.

Organizers

Joan Conaway

Joan Conaway, Stowers Institute for Medical Research

Bing Ren

Bing Ren, University of California, San Diego