# Role of BHC80 in spermatogenesis

> **NIH NIH R03** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $81,000

## Abstract

PROJECT SUMMARY
Spermatogenesis is a highly coordinated process that starts with spermatogonial stem cells (SSCs),
which self-renew and differentiate into more mature germ cells to sustain male fertility throughout life.
Within the seminiferous epithelium, germ cell development depends on a specific environment created by
somatic cells, which provide a number of growth and differentiation factors. The interplay between
microenvironment and germ cells is crucial for sperm production, as dysregulation of this process will
lead to sterility. Our work focuses on the function and regulation of the transcription factor RBPJ in
Sertoli cells. RBPJ is the main mediator of NOTCH signaling, and belongs to a repressor/activator complex
at the promoter of target genes. Depending on the cellular context, RBPJ indirectly represses or allows the
expression of genes such as Gdnf and Cyp26b1, which are critical for the maintenance of undifferentiated
spermatogonia. Through a yeast-2-hybrid assay, we have discovered a novel RBPJ-interacting protein in
Sertoli cells, called BHC80. BHC80 is a histone reader that presumably stabilizes KDM1A (a H3K4me2
demethylase) at the repressor complex. BHC80 is encoded by the gene Phf21a and is highly expressed in
the brain and testis. In humans, mutations (usually microdeletions) in the Phf21a gene cause Potocki-Saffer
syndrome, which is associated with severe intellectual disabilities and craniofacial anomalies. In order to
understand how BHC80 regulates RBPJ activity, and to study the function of BHC80 and its target genes
beyond NOTCH signaling in Sertoli cells, we will establish a mouse Sertoli cell-specific knockout of
Phf21a and characterize its testicular phenotype. To produce the floxed Phf21a mouse, we will employ a
novel CRISPR/Cas9 technique called DECAI, which is predicted to generate a higher ratio of pups
containing the insert. This small research project aligns with NICHD’s Fertility and Infertility’s mission and
its high-priority research area of genetic basis of idiopathic male infertility. It is intended for the development
of a research methodology, and the established floxed model will be an important resource for research
in the areas of reproductive biology, intellectual disabilities and craniofacial anomalies. !

## Key facts

- **NIH application ID:** 9953312
- **Project number:** 1R03HD101650-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Marie-Claude Catherine Hofmann
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,000
- **Award type:** 1
- **Project period:** 2020-03-11 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953312

## Citation

> US National Institutes of Health, RePORTER application 9953312, Role of BHC80 in spermatogenesis (1R03HD101650-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9953312. Licensed CC0.

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