# Systematic elucidation of allele specific proteome at Imprint Control Regions

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $355,950

## Abstract

Project Summary
Genomic imprinting is an epigenetic process resulting in the monoallelic, parent-of-origin-
specific expression of a small subset of genes (<150) in the mammalian genome.Imprinted
genes are essentialduring and post-embryonic development and defects in dosage imbalance of
imprinted genes result in complex rare epigenetic diseases generally involving multiple tissues,
named Imprinting Disorders(IDs).Within an imprinted domain, DNA sequence elements named
Imprinting Control Regions(ICRs) regulate imprinted expression of genes and are differentially
marked by DNA methylation during gametogenesis when maternal and paternal genomes are
still in distinct partitions.How ICRs bring about imprinted gene expression and what trans acting
protein factors and complexes that occupy parental ICR alleles are required for establishment
and maintenance of imprinted patterns of gene expression still remain mostly unknown. The
main objective of this proposalis to elucidate the protein assemblies on parental alleles of
imprint control regions to understand how cis regulation by trans factors maintain the parent-of-
origin expression. We will accomplish this by employing the relatively new methodologies of
locus specific genome targeting and intracellular protein labeling. In the first aim, multiple
transgenic reciprocal hybrid ES lines will be utilized to decipher the maternal or paternal ICR
allele specific protein complexes. In the second aim we will test how depletion of cis acting
RNAs and associated loss of ICR enhancer function affects the protein complexes on maternal
allele.Finally, in the third aim, we will focus to quantitate the molecular proteomic changes in ES
cells with uniparental disomies to understand ICR functions in imprinted disorders. Together,
our studies will i) illuminate parental ICR allele specific protein complexes, ii) define ICR derived
cis elements required for their protein complex localization/imprinting function and iii) define
differential protein complexes in uniparental chromosomal disomies. Findings from this study
will lead to a greater understanding of the trans protein factors at Imprint Control Regions and
will provide mechanistic details into cis regulation of ICR functions in an unbiased manner.

## Key facts

- **NIH application ID:** 9865070
- **Project number:** 1R01GM135377-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Satya K. Kota
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $355,950
- **Award type:** 1
- **Project period:** 2020-04-09 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9865070

## Citation

> US National Institutes of Health, RePORTER application 9865070, Systematic elucidation of allele specific proteome at Imprint Control Regions (1R01GM135377-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9865070. Licensed CC0.

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