# Characterization of a novel family of human transcription factors that bind at +240 downstream of the transcription start site.

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $330,000

## Abstract

Our study focuses on a family of human C2H2 zinc finger proteins composed of ZFX, ZFY, and ZNF711
which are expressed in all human cell types. In our preliminary studies, we show that deletion of ZFX
family members has severe detrimental consequences on cell proliferation. We have performed ChIP-
seq assays for ZFX, ZFY, and ZNF711 in several different human cell lines. Interestingly, we found that
these TFs have identical binding patterns at the same CpG island promoter regions, with an average peak
of binding at +240bp downstream of the transcription start site. Although their protein structure suggests
that ZFX, ZFY, and ZNF711 are transcriptional regulators, the mechanisms by which they influence
transcription have not yet been elucidated. Our preliminary results suggest that the ZXF family members
are important regulators of the human transcriptome. A failure to properly regulate the
transcriptome can lead to many types of human disease. Therefore, a thorough characterization of this
family of TFs is of critical importance. Two of the family members (ZFX and ZFY) are essentially identical
proteins encoded on either the X or Y chromosome, whereas ZNF711 has 67% overall similarity with ZFX
and 87% similarity in the zinc finger domain. Because ZFX and ZFY are basically identical proteins, we will
focus on a comparison of ZFX and ZNF711 using a female cell line (which lacks ZFY). We propose to
characterize the mechanisms by which these factors regulate transcription using a 3-pronged approach. In
Aim 1, we will perform detailed investigations of ZFX and ZNF711 binding to determine how these
transcription factors are recruited to CpG island promoters. In Aim 2, we will identify critical regulatory
domains and interacting proteins of ZFX and ZNF711. In Aim 3, we will characterize the mechanism by
which ZFX and ZNF711 mediate transcriptional regulation. Importantly, each of the Aims can be performed
independently of the others and can begin immediately. Through the combination of Aims 1-3, we will
thoroughly characterize the function of the ZFX family using epigenomic, proteomic, and transcriptomic
approaches. Completion of our proposed studies will provide new insights into transcriptional
regulation and chromatin structure at human CpG island promoters.

## Key facts

- **NIH application ID:** 10136032
- **Project number:** 5R01GM133450-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** PEGGY J Farnham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $330,000
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136032

## Citation

> US National Institutes of Health, RePORTER application 10136032, Characterization of a novel family of human transcription factors that bind at +240 downstream of the transcription start site. (5R01GM133450-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136032. Licensed CC0.

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