In order to function correctly, cells must regulate gene expression; chemical modification of DNA is an important method by which they achieve this. For example, cytosine can be methylated to form 5-methylcytosine (5mC), a repressive epigenetic marker. 5mC can be oxidized by Ten-Eleven-Translocation (TET) enzymes to produce additional forms of cytosine. One of these derivatives, 5-hydroxymethylcytosine (5hmC), is an activator of gene expression and ͏can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Subsequently, 5caC is excised and replaced with unmodified cytosine. This process by which 5mC is converted back to cytosine is known as active demethylation (AD).
Improper control of methylation and demethylation can impair development and is a hallmark of many cancers. Ubiquitin-like Modifier with PHD and Ring Finger Domain 2 (UHRF2) is a DNA-interacting protein that plays an important but poorly characterized role in active demethylation. Previous work suggests that UHRF2 is required for the maintenance of 5hmC levels in somatic cells but does not demonstrate a mechanism. Furthermore, a paralog of this protein, UHRF1, binds to 5mC via its Set and Ring Associated (SRA) domain to preserve methylation levels in DNA. Thus, we proposed a related model where UHRF2 binds to 5hmC via its SRA domain and prevents further oxidation by TET enzymes. 
In this study, we overexpressed UHRF2 and TET2 in wild-type U2OS (human osteosarcoma) cells and U2OS cells with endogenous UHRF2 expression knocked out. We also conducted domain-deletion experiments to determine which domains of UHRF2 are required to preserve 5hmC levels.
As expected, we demonstrated that excess TET2 increased 5hmC levels in both cell lines, but concurrent overexpression of UHRF2 appeared to amplify this effect. We also determined that the plant homeodomain (PHD), tandem Tudor domain (TTD), and SRA domain are each necessary for UHRF2 to preserve 5hmC levels. Furthermore, we found that simultaneous overexpression of TET2 and UHRF2 increased levels of 5fC more than overexpressing TET2 alone, suggesting that UHRF2 may have a more complex role in regulating the AD cycle. Eventually, a better understanding of UHRF2 function will elucidate its role in cancer and may guide future research and therapeutics.

The epigenetic modifier UHRF2 has a complex role in 5hmC maintenance

 Hematology / Oncology / Pathology

poster

Welcome to the **largest national, multi-specialty research** event featuring research from nearly 700 medical students, residents, fellows, and international medical graduates.

Use the buttons below or navigation menu to access the event.
 


[![](https://assets.underline.io/uploads/markdown_image/1/image/3e33a8c754cc49610b30950617d813e7.png)](https://underline.io/events/434/sessions?searchGroup=all)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/551404d429c4e274f9a54cbdd7081918.png)](https://underline.io/events/434/posters?searchGroup=all)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/677d92f566b880cebd36905fc738fc10.png)](https://underline.io/events/434/lounge)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/c7392833c7261c3874c5b43fa2f4df19.png)](https://underline.io/events/434/help-desk)
 

#### Event Details

The 2023 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. **Log in at any time throughout the event to:**

* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research
* **Attend education sessions** with physician experts on key research topics

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges, and compete to win a $10,000 grand prize sponsored by Laurel Road. 

### Grand Prize Sponsor

AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in the judging or scoring process to select the winner. The winner will be announced on February 4, 2024 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)

**There is no registration fee for this event! **

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals.

**Please use this link [here](https://www.ama-assn.org/about/events/ama-research-challenge) to register for free.**

Registration Is Required

AMA Research Challenge 2023

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters, score posters in the semifinals (an AMA member exclusive opportunity) and attend education sessions with experienced physicians to learn tips to advance your research and career. 

Neetij Krishnan

1

SHORT BIO

Presentations

The epigenetic modifier UHRF2 has a complex role in 5hmC maintenance

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES