Andrew Chess, MD
img_Andrew Chess
PROFESSOR | Genetics and Genomic Sciences
PROFESSOR | Cell, Developmental & Regenerative Biology
PROFESSOR | Neuroscience
Research Topics
Epigenetics, Genetics, Human Genetics and Genetic Disorders
Multi-Disciplinary Training Area
Genetics and Genomic Sciences [GGS]

A longstanding interest of the Chess lab is the study of unusual mechanisms involved in regulating gene expression. Recently we have been developing approaches to allow the study of epigenetic regulation at the scale of the entire human genome. Understanding of epigenetic mechanisms is essential to understanding normal development and disease. The Chess Lab website will have more information ( ).


DNA Methylation


DNA methylation stands out amongst epigenetic marks in that it is a covalent modification of the DNA molecule itself (albeit a modification that doesn’t change the DNA sequence). For DNA methylation (specifically methylation of cytosines within CpG dinucleotides) there is a known mechanism for replicating the mark. The DNA methyltransferase I encodes a protein which recognizes hemi-methylated DNA (arising from the replication of a double-stranded methylated DNA molecule) and methylates the other strand. Genome-scale analyses of DNA methylation have led to the first demonstration of methylation of the gene body (the entire transcribed region) of mammalian genes. This work also showed more methylation on the active X than the inactive X in female cells (Hellman and Chess, 2007). These observations resulted from our decision to consider all types of CpGs rather than earlier studies that focused on CpG islands. Gene body methylation, which is present in plant genomes as well as animal genomes, adds another layer of complexity to the role of DNA methylation in regulation of the genome.


Polymorphism in DNA sequence is well known, but until recently the potential for DNA methylation polymorphism was not explored. We and others have found evidence for such DNA methylation polymorphism. Our genome-scale analyses have revealed an interesting interplay between DNA sequence polymorphism and DNA methylation polymorphism (Hellman and Chess, 2010).


Random monoallelic expression


Monoallelic expression represents a good model system for studying epigenetics because it requires the differential treatment of two alleles (which are sometimes identical in sequence). Monoallelic expression with random choice between the maternal and paternal alleles defines an unusual class of genes comprising X-inactivated genes and a few autosomal gene-families. Using a genome-wide approach, a few years ago we assessed allele-specific transcription of ~4,000 human genes in clonal cell lines and found that over 300 were subject to random monoallelic expression (Gimelbrant et al., 2007). For a majority of monoallelic genes, they observed some clonal lines displaying biallelic expression. Clonal cell lines reflect an independent choice to express the maternal, the paternal, or both alleles for each of these genes. This can lead to differences in expressed protein sequence, and to differences in levels of gene expression.


Widespread monoallelic expression suggests a mechanism that generates diversity in individual human cells and their clonal descendants. We have extended these observations to the mouse genome (in preparation, 2011).


Some other highlights


Discovery of allelic exclusion of mouse odorant receptor genes (Chess et al., 1996).


Identification of the odorant receptor gene family in Drosophila, along with the demonstration that different olfactory neurons express different receptors and converge in their projections to the antennal lobe creating a spatial representation of olfactory space (Gao and Chess, 1999; Gao et al., 2000).


Elucidation of a role for asynchronous replication in immunoglobulin gene allelic exclusion (Mostoslavsky et al., 2001).


Demonstration of chromosome-level coordination of replication timing in mouse and human cells (Singh et al., 2003; Ensminger and Chess, 2004).


Cloning of a mouse from an olfactory neuron (Eggan et al., 2004).


Insights into the evolution of the odorant receptor gene family in humans (Gimelbrant et al., 2004).


Uncovering a role for alternative splicing in the specification of unique identity of neurons (Neves et al., 2004; Zhan et al., 2004).


Discovery of a non-coding RNAs associated with nuclear structures, and the demonstration that one of them, NEAT1, plays a structural role in the nuclear parapspeckle (Hutchinson et al., 2007; Clemson et al., 2009).


Selected Publications

Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders. Yan Xia, Cuihua Xia, Yi Jiang, Yu Chen, Jiaqi Zhou, Rujia Dai, Cong Han, Zhongzheng Mao, Chunyu Liu, Chao Chen, Schahram Akbarian, Alexej Abyzov, Nadav Ahituv, Dhivya Arasappan, Jose Juan Almagro Armenteros, Brian J. Beliveau, Jaroslav Bendl, Sabina Berretta, Rahul A. Bharadwaj, Arjun Bhattacharya, Lucy Bicks, Kristen Brennand, Davide Capauto, Frances A. Champagne, Tanima Chatterjee, Chris Chatzinakos, Yuhang Chen, H. Isaac Chen, Yuyan Cheng, Lijun Cheng, Andrew Chess, Jo Fan Chien, Zhiyuan Chu, Declan Clarke, Ashley Clement, Leonardo Collado-Torres, Gregory M. Cooper, Nikolaos P. Daskalakis, John F. Fullard, Kiran Girdhar, Vahram Haroutunian, Gabriel E. Hoffman, Alex Kozlenkov, Donghoon Lee, Dalila Pinto, Towfique Raj, Panos Roussos, Robert Sebra, Georgios Voloudakis, Biao Zeng. Science Translational Medicine

Genomic data resources of the Brain Somatic Mosaicism Network for neuropsychiatric diseases. McKinzie K.A. Garrison, Yeongjun Jang, Taejeong Bae, Adriana Cherskov, Sarah B. Emery, Liana Fasching, Attila Jones, John B. Moldovan, Cindy Molitor, Sirisha Pochareddy, Mette A. Peters, Joo Heon Shin, Yifan Wang, Xiaoxu Yang, Schahram Akbarian, Andrew Chess, Fred H. Gage, Joseph G. Gleeson, Jeffrey M. Kidd, Michael McConnell, Ryan E. Mills, John V. Moran, Peter J. Park, Nenad Sestan, Alexander E. Urban, Flora M. Vaccarino, Christopher A. Walsh, Daniel R. Weinberger, Sarah J. Wheelan, Alexej Abyzov, Aitor Serres Amero, Danny Antaki, Dan Averbuj, Laurel Ball, Sara Bizzotto, Craig Bohrson, Rebeca Borges-Monroy, Martin Breuss, Sean Cho, Chong Chu, Changuk Chung, Isidro Cortes-Ciriano, Michael Coulter, Kenneth Daily, Caroline Dias, Alissa D’Gama, Yanmei Dou, Jennifer Erwin, Diane A. Flasch, Trenton J. Frisbie, Alon Galor, Javier Ganz, Doga Gulhan, Robert Hill, August Yue Huang, Andrew Jaffe, Alexandre Jourdon, David Juan, Sattar Khoshkhoo, Sonia Kim, Huira C. Kopera, Kenneth Y. Kwan, Minseok Kwon, Ben Langmead, Eunjung Alice Lee, Sara Linker, Irene Lobon, Michael A. Lodato, Lovelace J. Luquette, Gary Mathern, Tomas Marques-Bonet, Eduardo A. Maury, Michael Miller, Manuel Solis Moruno, Rujuta Narurkar, Apua Paquola, Reenal Pattni, Raquel Garcia Perez, Inna Povolotskaya, Patrick Reed, Rachel Rodin, Chaggai Rosenbluh, Soraya Scuderi, Maxwell Sherman, Richard Straub, Eduardo Soriano, Chen Sun, Jeremy Thorpe, Vinay Viswanadham, Meiyan Wang, Xuefang Zhao, Bo Zhou, Weichen Zhou, Zinan Zhou, Xiaowei Zhu. Scientific data

Author Correction: Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia (Nature Neuroscience, (2021), 24, 2, (186-196), 10.1038/s41593-020-00767-4). Xiaowei Zhu, Bo Zhou, Reenal Pattni, Kelly Gleason, Chunfeng Tan, Agnieszka Kalinowski, Steven Sloan, Anna Sophie Fiston-Lavier, Jessica Mariani, Dmitri Petrov, Ben A. Barres, Laramie Duncan, Alexej Abyzov, Hannes Vogel, Xiaowei Zhu, Bo Zhou, Alexander Urban, Christopher Walsh, Javier Ganz, Mollie Woodworth, Pengpeng Li, Rachel Rodin, Robert Hill, Sara Bizzotto, Zinan Zhou, Alice Lee, Alissa D’Gama, Alon Galor, Craig Bohrson, Daniel Kwon, Doga Gulhan, Elaine Lim, Isidro Cortes, Joe Luquette, Maxwell Sherman, Michael Coulter, Michael Lodato, Peter Park, Rebeca Monroy, Sonia Kim, Yanmei Dou, Andrew Chess, Attila Jones, Chaggai Rosenbluh, Schahram Akbarian, Ben Langmead, Jeremy Thorpe, Jonathan Pevsner, Rob Scharpf, Simone Tomasi. Nature Neuroscience

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Dr. Chess has not yet completed reporting of Industry relationships.

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