October 2011

The many modes of gene regulation

Epigenetics, chromatin and beyond

Meetings_Gene_RegulationInvestigations in recent years have illuminated a multiplicity of strategies for regulating gene expression. From chromatin structure to noncoding RNAs to promoter-proximal pausing of RNA polymerase II, it is clear that cells have evolved a sophisticated and diverse tool kit for modulating transcription output. The 2012 annual meeting session on gene regulation will showcase the wide array of approaches, including structural biology, genetics, genomics and proteomics. In addition, speakers will describe gene regulation during cell differentiation and development and responses to stimuli.

Epigenetic readers, writers and erasers 

Epigenetic changes to chromatin and DNA underlie developmental processes. The first session focuses on histone modifications and their recognition as well as the processes affected by these marks. The session begins with a talk by Yang Shi (Harvard Medical School and Children’s Hospital Boston), who will present work on understanding mechanisms that regulate histone methylation dynamics and on effector, also known as reader, proteins that recognize histone methylation.

Dinshaw Patel (Sloan-Kettering Cancer Center) will present insights into how these covalent modifications are recognized and deposited from a structural perspective, providing a mechanistic basis for their function.

The importance of regulated modifications of histones during vertebrate development will be addressed by Joanna Wysocka (Stanford University), whose work has elucidated the roles of several readers and writers of epigenetic marks during cell-fate specification.

Looking under the hood to dissect transcription mechanisms 

The second session will delve into fundamental mechanisms in gene regulation. Joan Conaway (Stowers Institute for Medical Research) will focus on the Mediator complex, which bridges interactions between transcription activators and RNA polymerase II, helping to recruit polymerase to a gene’s promoter. New results from the Conaway lab reveal that Mediator also can enhance transcription elongation through stimulating the release of paused Pol II.

Dylan Taatjes (University of Colorado at Boulder) will provide additional insights into Mediator and its interactions with the transcription machinery. Structural analyses of Mediator in complex with various transcription activators shed light on how Mediator translates activator binding to Pol II and the general transcription factors to influence transcription.

In addition to protein factors, RNA species are emerging as important regulators of gene expression. Ramin Shiekhettar (Wistar Institute) will present his recent findings on the roles of long noncoding RNAs in tuning gene expression. Sheikhettar will discuss the interesting relationships between transcriptional enhancers and noncoding RNA species that are generated from these enhancers under tissue-specific conditions.

Putting the puzzle pieces together 

The third session, “Transcriptional Regulation During Growth and Development,” is devoted to how gene regulatory mechanisms are played out in vivo. Joaquin Espinosa (University of Colorado at Boulder) will describe his work on transcription regulation by the p53 network. Activation of p53 can lead to distinct outcomes depending on the signal and cell context, suggesting that cells employ different transcription co-regulators to tailor the p53 response to oncogenic stimuli.

Susan Mango (Harvard University) will describe the role of the FoxA family of transcription factors in establishing the foregut during development. Mango’s findings illuminate how these factors provide the foundation for the transcription pathways that govern organ development in the C. elegans foregut. 

Cell differentiation involves an integration of information provided by transcription-factor activity and chromatin structure. Ken Zaret (The University of Pennsylvania) will discuss the role of pioneer transcription factors in mammalian cell differentiation, describing how they uncover specific segments of the genome to make them accessible and amenable for activation.

Nucleosomes vs. the transcription machinery 

The final session, “Interplay Between Chromatin Structure and the Transcription Machinery,” will expand on the idea that the transcription machinery can serve as a barrier to chromatin formation. Karen Adelman (National Institute of Environmental Health Sciences) will describe how the pausing of Pol II during early elongation prevents nucleosome assembly near promoters, thereby enhancing gene expression and poising genes for robust activation.

Gordon Hager (National Cancer Institute) will discuss recent findings that signal-dependent binding of nuclear receptors to DNA often targets sites of pre-opened chromatin. This suggests that the pre-existing chromatin structure in a given cell type or condition can affect the activity of nuclear receptors significantly.

Transcription factors themselves also can be targets of post-translational modifications. Or Gozani (Stanford University) will describe how lysine methylation of both histones and transcription factors is regulated to affect gene expression.

Meetings_Gene_Regulation_Karen_ADELMANMeetings_Gene_Regulation_Shi_YangKaren Adelman (adelmank@niehs.nih.gov) is a principal investigator at the National Institute of Environmental Health Sciences, and Yang Shi (yang_shi@hms.harvard.edu) is a professor at Harvard Medical School and Children’s Hospital Boston. 

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