# ERK mediated regulation of RbAp46/48 during female germ cell development

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $326,648

## Abstract

PROJECT SUMMARY
ERK (Extracellular signal Regulated Kinase) signaling is critical for female fertility and normal embryonic
morphogenesis. Two key events that ERK signaling regulates to control female fertility are (a) progression of
female meiosis I and (b) resumption of oocyte meiosis after prolonged arrest (also called oocyte meiotic
maturation). Stereotypical execution of meiosis I requires that homologous chromosomes pair, align, form
physical connections, exchange genetic information and segregate homologs into gametes. Mis-regulation of
any of these steps results in failures in chromosome segregation causing severe developmental disorders, e.g.,
the Down’s syndrome. We find that loss of erk signaling results in failure of chromosomes to maintain synapsis
causing embryonic lethality. In addition to meiosis I progression, ERK activation is essential for oocyte
development and resumption after prolonged arrest in meiosis I. Oocytes arrest in meiosis I for decades in
humans, an event that is critical for reproductive fitness of the species. Meiosis I is then resumed as the oocyte
matures and the process of oocyte meiotic resumption or maturation is coordinated through hormonal signaling
and ERK activation. Failure of oocytes to either undergo arrest or fail in meiotic maturation results in female
sterility or birth defects. Inappropriate ERK signaling results in defects in oocyte meiotic maturation causing
sterility or birth defects. Determining the proteins that ERK phosphorylates and regulates to mediate these two
events that control female fertility and embryonic morphogenesis will guide not only our understanding of female
reproduction but also provide effective measures to modulate the pathway for interventions. We identified two
proteins RbAp46 and RbAp48 as ERK substrates that regulate chromosome dynamics during meiosis I and
oocyte meiotic maturation respectively. RbAp46/RbAp48 are paralogous proteins that function as histone
chaperones in the Polycomb Repressive Complex 2 (PRC2) and Nucelosome Remodeling Complex (NuRD) in
worms and mammals to regulate epigenetic marks and transcriptional silencing, this is the first description of (i)
their regulation by ERK signaling and (ii) their function in regulating female meiosis I and oocyte maturation. The
goal of this proposal is to understand the genetic and molecular basis of these functions.

## Key facts

- **NIH application ID:** 10219320
- **Project number:** 5R01HD101269-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Swathi Arur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,648
- **Award type:** 5
- **Project period:** 2020-07-18 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219320

## Citation

> US National Institutes of Health, RePORTER application 10219320, ERK mediated regulation of RbAp46/48 during female germ cell development (5R01HD101269-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10219320. Licensed CC0.

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