about us
We are interested in understanding how the environment affects the epigenome to elicit changes that can be inherited from one generation to the next, and how these changes can result in disease states. We are also studying how effects of the environment on the epigenome respond to genetic variation in the non-coding genome. In particular, we are currently studying how chemicals present in the environment affect the location of CTCF in the genome to alter the three-dimensional organization of the chromosomes in germline cells, how these changes are transmitted to the embryo after fertilization, how they are propagated during differentiation of various cell lineages, and how these alterations cause obesity and autism in a manner that depends on variation in the non-coding genome
3D chromatin organization
transgenerational epigenetics
autism spectrum disorders
The DNA is arranged in a specific manner in the 3D space of the nucleus. This arrangement is partly a consequence of the transcriptional state of the chromatin. In addition, the CTCF protein and the cohesin complex for loops between specific sites in the chromatin. These loops help regulate enhancer-promoter interactions. Since may of these loops are cell-type specific, they help orchestrate distinct patterns of gene expression. As a consequence, CTCF and cohesin help establish different cell lineages during development. You can click on the icon above to learn more about this topic and what we are doing in the lab to understand how CTCF works in the nucleus of eukaryotic cells
The genome of the parents is transmitted to their progeny after fertilization. In addition, environmental factors can alter the epigenome and these epigenetic changes can be also transmitted to the next generation. Therefore, the environment e.g. stress, diet, and chemicals we encounter in our daily life, can affect the epigenome of the gametes in each generation and affect the health of the progeny. How this happens, and whether it is reversible, is one of the big questions in biology today. Click on the icon above to learn more about this topic what we are doing to answer the role of changes in the germ cell epigenome that results in obesity that is transited through many generations
One in 68 newborns in the US has autism, making this, together with Alzheimer's, one of the most important challenges in medicine today. Research in the last 10 years has shown that many cases of autism are the result of new mutations in the gametes of the parents. However, many autism cases are not the result of mutations in protein-coding genes. Both in humans and laboratory animals exposure of the embryo to chemicals such as BPA and even anesthetic gases results in autism symptoms in the progeny. Click on the icon above to learn how we are trying to understand this problem by studying the effect of environmental chemicals and CTCF on brain development
recent papers
Below is a sample of recent manuscripts that reflect the current interests of the lab. Hovering the mouse cursor over each icon displays the abstract for each manuscript. A pdf file of the paper can be downloaded by clicking on the corresponding icon. A more extensive collection of pdf files for most of our published work can be found at the Publications link
Jung et al. Transgenerational inheritance of BPA-induced obesity correlates with transmission of new CTCF sites in the Fto gene. SNPs in non-coding regions of the FTO gene predispose to obesity in humans. We show that exposure of pregnant females to BPA results in the binding of CTCF to a new enhancer in the Fto gene, causing obesity that can be transmitted for 6 generations
Nichols and Corces. Principles of 3D Compartmentalization of the Human Genome. Here we show that, instead of the classical active and inactive compartments, cells have at least 4 different compartments that vary in the types of histone modifications. The nature of these compartments can be different in different cells, and even in different chromosomes of a specific cell
Jung et al. Maintenance of CTCF- and transcription factor-mediated interactions from the gametes to the early mouse embryo. This manuscript is the basis for most of our ideas on transgenerational epigenetic inheritance. The paper shows that sperm and oocytes have bound transcription factors at many sites in the genome, and many of these sites are maintained in the embryo after fertilization
Rowley, M. J., and Corces, V. G. (2018). Organizational Principles of 3D Genome Architecture. This is a review of the mechanisms by which the organization of the chromatin fiber in the 3D nucleus is established and maintained. The review offers a new interpretation of Hi-C data and proposes a view of 3D nuclear architecture that is different from the prevalent and popular view
Lyu et al. Architectural proteins and pluripotency factors cooperate to orchestrate the transcriptional response of hESCs to temperature stress. The location of CTCF in the genome changes when cells are exposed to temperature stress, resulting in the formation of new loops and dismissal of existing ones. This results in changes in enhancer-promoter interactions and new patterns of gene expression
Xu and Corces. Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF-cohesin sites. Here we find that the DNA at many sites in the genome is hemimethylated and this state is propagated during DNA replication. These sites are enriched at CTCF sites, at the border of the nucleosomes flanking the protein. The hemimethylation is required for proper interaction between CTCF sites in the genome
people
We are a team of smart and dedicated scientists a little obsessed with figuring out how things work in the nucleus
Victor Corces, writes MIRA grants, NIGMS cuts the budget by 90%, and then he has to write more grants
Samantha Forestier, Research Specialist, studies the effect of environmental chemicals in autism
Yoonhee Jung, Postdoctoral Fellow, studies the transgenerational transmission of BPA-induced obesity
Pawel Piwko, Postdoctoral Fellow, studies the mechanisms by which mutations in CTCF cause autism
Daniel Ruiz, Postdoctoral Fellow, studies mechanisms by which PBBs affects the reproductive system
Hsio-Lin Wang, Postdoctoral Fellow, studies the effects of general anesthetics in pregnant females and their role in autism
Jian-Feng Xiang studies mechanisms by which CTCF cooperates with other proteins to regulate 3D genome organization
cover art
This is a sample of our contribution to the covers of the journal issues where our papers were published
underwater photography
When the time is right and he doesn't have to worry about the budget of his MIRA grant getting cut, leaving his lab with no money to do experiments, Victor likes to go scuba diving. His favorite places to dive are Indonesia and the Philippines. When diving, Victor likes to take pictures, mostly of things no bigger than 10 mm. Otherwise is not challenging enough. He is happiest when he can get a perfectly black background. His dream is to live in the beach below with a nucleus, an unlimited supply of nitrox tanks, and a laptop. When he is not diving, he can then write MIRA grants so that bureaucrats at NIGMS can cut the budgets and leave no funds to do experiments. Here you can see some of his pictures, mostly of tiny nudibrachs
©2020 Astur Designs. Made with and recycled pixels
