# Studies on Epigenetically Active Latent Chromatin Maintenance

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $532,446

## Abstract

Deregulation of genome interactions through mutations at regulatory elements or mutation of responsible
cellular nuclear enzymes result in multiple disorders. Although the significance of proper genomic-genomic
interactions has been seen from disease phenotypes, the underlying molecular mechanisms of genomic looping
regulation and the direct outcome of transcription are still not well connected. This partly stems from the highly
complex nature of cellular promoter regulation, since it is controlled by multiple transcriptional factors and enhancer
elements with significant noise within cell populations.
 Transcriptomics, genomics, and proteomics studies with recombinant Kaposi's sarcoma-associated
herpesvirus (KSHV) episomes identified that the host cellular ChAHP (CHD4, ADNP, HP1) protein complex forms a
stable protein complex with KSHV latency associated nuclear antigen (LANA) and plays essential roles in maintaining
the inducibility of latent viral chromatin. The ChAHP complex is known to restrict cellular enhancer accessibility and
regulates cell lineage, although how the protein complex regulates enhancer-promoter interaction remains unknown.
Here, we hypothesize that the KSHV latency-lytic switch is a product of enhancer-promoter interactions regulated by
the LANA-ChAHP complex. In this application, we will study how the KSHV episome is maintained as an inducible
episome and if we can target the protein complex for therapeutic intervention. The molecular action of the
LANA/ChAHP protein complex will be studied from three different perspectives; (i) biochemical, (ii) genetic, and (iii)
protein complex structure. By taking advantage of defined enhancer-promoter pairs and convenient inducible mini
viral chromatin, we will study enhancer-promoter regulations by dissecting ChAHP protein complex function. The
proposed studies should not only benefit the understanding of the KSHV latency-lytic switch, but also provide insight
into cellular inducible enhancer regulatory mechanisms.

## Key facts

- **NIH application ID:** 10756993
- **Project number:** 5R01AI167663-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Yoshihiro Izumiya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $532,446
- **Award type:** 5
- **Project period:** 2022-02-10 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756993

## Citation

> US National Institutes of Health, RePORTER application 10756993, Studies on Epigenetically Active Latent Chromatin Maintenance (5R01AI167663-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10756993. Licensed CC0.

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