# Defining the Transcriptional Regulation and Genomic Organization of FAIM3 and PIGR, Human Ig Receptors Involved in Immunity, Auto-Immune Disease, and Lymphoma

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2020 · $4,210

## Abstract

ABSTRACT
A fundamental outstanding question in cellular development remains how epigenetic mechanisms of gene
regulation are coordinated during development and their role in disease. Genome structure and topology, local
chromatin landscape, and non-coding RNAs all contribute to epigenetic transcriptional regulation. Moreover,
alterations in these elements or factors can perturb gene expression and promote disease pathogenesis, as
shown for B cell lymphoma (Koues et al, Immunity 2015). While the general principles of these mechanisms
are widely accepted, the specific identity and interplay of these elements at individual gene loci is largely
unknown. Therefore, the proposed studies will define regulatory interactions at a single locus containing two
genes that are essential for normal immune function and, when deregulated, promote auto-immunity or cancer.
FAIM3 (TOSO, FCMR) is an IgM receptor expressed in innate and adaptive immune cells, and PIGR encodes
the IgA receptor and secreted IgA in mucosal epithelial cells. Importantly, preliminary studies show that
regulatory elements and a lncRNA in this locus are deregulated in B cell lymphomas and leukemia. By
elucidating the regulatory mechanisms that control expression of these genes in a cell-specific manner, the key
elements necessary for lineage specificity and how these regulatory mechanisms are corrupted in lymphoid
cancers will be revealed. Aim 1 will define the genomic organization and 3-dimensional structure of the locus.
In addition, Aim 1 studies will determine the contribution of regulatory elements to maintaining this structure
and transcriptional control of FAIM3, PIGR, and neighboring genes. Aim 2 will elucidate the transcription
factors that serve as key regulators of FAIM3 and PIGR and determine how genetic polymorphisms and
mutations alter this regulation through perturbation of transcription factor binding. Aim 3 will characterize a
novel long non-coding RNA, confirming its full sequence, verifying its exonic structure, and determining
whether it contributes to the transcriptional control of FAIM3 or PIGR. Upon completion of these studies, the
regulatory elements and mechanisms that control the cell-specific expression of FAIM3 and PIGR will be
defined, as will how these genes are altered in lymphoid cancer. The impact of these studies will reach beyond
a single gene locus, by providing a window into the intricate interplay of epigenetic and genetic mechanisms of
gene regulation and deregulation in normal development and cancer.

## Key facts

- **NIH application ID:** 9938492
- **Project number:** 5F31CA221012-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jared Andrews
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $4,210
- **Award type:** 5
- **Project period:** 2017-07-01 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938492

## Citation

> US National Institutes of Health, RePORTER application 9938492, Defining the Transcriptional Regulation and Genomic Organization of FAIM3 and PIGR, Human Ig Receptors Involved in Immunity, Auto-Immune Disease, and Lymphoma (5F31CA221012-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9938492. Licensed CC0.

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