# Transcriptional Regulation by Epigenetic Factors

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $319,800

## Abstract

Project Summary:
 Cell memory plays a key role during differentiation and disease. It relies on epigenetic inheritance
that is essential to propagate gene expression program through cell generation, in large part through
maintaining the structure of chromatin in daughter cell. DNA replication is the major obstacle in
conservation of chromatin structure. During replication, most proteins are thought to dissociate from
DNA. A few molecules may remain associated with DNA, thus marking DNA regulatory elements for
future maturation of chromatin into an open or compact conformation. The identity of these epigenetic
marks is unknown. The best candidates are thought to be modified histones because they are assumed
to transfer from the parental to daughter nucleosomes on nascent DNA. However, until recently, there
were no experimental approaches to directly examine neither the nature of epigenetic marks, nor the
order and timing of recruitment of chromosomal proteins to DNA following replication. Similarly, we know
very little about how and when transcription resumes after DNA replication.
 We developed several new experimental approaches that allow addressing these key epigenetic
issues, and found that the structure of chromatin is not as severely disrupted as is currently suggested.
RNA Polymerase II and related general transcription and elongation factors are found on nascent DNA
just after replication. Moreover, even immature RNAs are found in the proximity to nascent DNA
suggesting that the RNA Pol II – RNA complex is able to survive DNA replication. We also found that
transcription resumes relatively quickly after DNA replication. Based on our published and preliminary
results, we propose to test a new epigenetic concept suggesting that once transcription is established,
most of the transcriptional apparatus may be associated with DNA through replication, thus serving as an
epigenetic mark for active genes. This possibility, however, conflicts with the conventional model
suggesting that transcription and replication complexes travel along DNA, since this will lead to collisions
of these protein complexes. To resolve this contradiction, we will test the hypothesis that the stability of
the transcriptional machinery through replication can be resolved if transcription and replication occur in
the stationary nuclear sub-domains, transcription and replication factories, and that DNA is reeled
through these protein factories. The results of these experiments will greatly contribute to our
understanding of the epigenetic processes, and may have a major impact on developing new
approaches in many biological and drug discovery fields.

## Key facts

- **NIH application ID:** 9915931
- **Project number:** 5R01GM075141-15
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** ALEXANDER M MAZO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $319,800
- **Award type:** 5
- **Project period:** 2005-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915931

## Citation

> US National Institutes of Health, RePORTER application 9915931, Transcriptional Regulation by Epigenetic Factors (5R01GM075141-15). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9915931. Licensed CC0.

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