# The BTB-ZF transcription factor, PLZF, requires YY1 to function

> **NIH NIH R21** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $235,500

## Abstract

Multiple BTB-ZF family transcription factors are essential for immune system development and/or essential
immune system functions. Some BTB-ZF transcription factors function, essentially, as “toggle switches” that
control key decision points during development. For example, the commitment of lymphocytes into the T or B
cell lineage requires LRF and commitment to the CD4 or CD8 T cell lineage requires ThPOK. Loss of
expression of the necessary BTB-ZF gene results in loss of cell lineage identify and dedifferentiation. Other
BTB-ZF family members control essential or unique effector functions of lymphocytes. Zbtb20, for example,
defines the function of natural IL-10 producing Tregs that are necessary for intestinal homeostasis. Bcl6 is
required for both the development of T follicular helper cells and germinal center B cells and Zbtb32 is required
for the proliferative burst of NK cells in response to viruses.
In this application, we show that the function of PLZF, the BTB-ZF transcription that controls the phenotype
and innate like effector functions of invariant natural killer (NKT) cells, requires Yin Yang 1 (YY1). YY1 is a
multi-faceted transcriptional regulator that belongs to the Polycomb protein family. YY1 is ubiquitously
expressed and is important for multiple, diverse biological processes. YY1 functions to regulate gene
transcription directly, via chromatin modifications, via direct interactions with other transcription factors and
even by impacting higher order functions such as by 3D chromatin looping or phase separation.
The goal of this application is to discriminate between different possible mechanisms by which YY1 controls
PLZF. In doing so, we anticipate that we will significantly advance the understanding of the regulation of BTB-
ZF master regulator transcription factors. We anticipate that we will also learn more about how the ubiquitously
expressed, multi-faceted transcription regulator YY1 controls discrete biological functions in different cell types.
Advances in these areas would fill substantial knowledge gaps and have the potential to impact both the
understanding of immune responses and, most likely, other biological systems where BTB-ZF genes play
important roles.
Overall, our application seeks to understand how a lineage specific transcription factor (PLZF) is controlled by
a ubiquitously expressed co-factor (YY1) resulting in lymphocyte subset discrete effector functions.

## Key facts

- **NIH application ID:** 10988734
- **Project number:** 1R21AI180563-01A1
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Derek B. Sant'Angelo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $235,500
- **Award type:** 1
- **Project period:** 2024-06-06 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988734

## Citation

> US National Institutes of Health, RePORTER application 10988734, The BTB-ZF transcription factor, PLZF, requires YY1 to function (1R21AI180563-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10988734. Licensed CC0.

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