# Understanding mechanisms of transcriptional regulation by chromatin adaptor proteins

> **NIH NIH K99** · ROCKEFELLER UNIVERSITY · 2021 · $100,000

## Abstract

PROJECT SUMMARY
Precise regulation of chromatin states is critical to many vital cellular processes, including differentiation and
proliferation. Chromatin misregulation has been associated with human diseases, such as cancer, intellectual
disabilities, and autoimmunity, among others. Understanding the mechanisms by which genomic access is
controlled at the level of chromatin is critical for revealing how cellular phenotypes are established and
maintained, and how these processes are altered in disease. This study focuses on elucidating the molecular
mechanisms by which the chromatin adaptor Menin coordinates protein complexes to transduce chromatin
signals into transcriptional outputs. This work will test the central hypothesis that context-specific functions of
Menin are dictated by its ability to bind distinct chromatin environments and recruit a variety of chromatin factors
in a highly regulated manner. During the mentored phase of the award, it will determine how Menin targets
specific genomic loci by integrating DNA-barcoded nucleosome libraries, epigenomics, and functional genomics
approaches. This multi-tiered approach will identify combinatorial histone modifications and transcription factors,
as well as delineate their biological relationships with Menin and how they contribute to its genomic localization
(Aim 1). It will also identify and comprehensively characterize chromatin proteins and complexes that mediate
regulatory functions of Menin at distinct cis-regulatory elements (Aim 2). During the independent phase of the
award, it will determine how recurrent MEN1 mutations affect Menin’s ability to target and shape the chromatin
landscape, as well as affect transcription (Aim 3). Furthermore, it will characterize the cellular and organismal
phenotypes elicited by endogenous expression of MEN1 mutant alleles. Successful completion of the proposed
studies will produce insights into how Menin regulates chromatin biology and transcription, and will provide a
greater understanding of the mechanisms by which disease-associated mutant Menin proteins promote disease.
Such knowledge could yield novel insights into the roles of chromatin and epigenetic regulators in normal
physiology and pathophysiology. The integrative approaches proposed here will serve as a valuable resource
for the wider scientific community interested in pursuing future studies of chromatin factors with presumed
adaptor/scaffolding functions that have not been studied previously due to limitations of current methods. They
will also serve as a platform for the PI to obtain new training in chromatin and chemical biology, biochemistry of
transcription, structural biology, and computational epigenomics. Such training will be critical for the development
of the PI’s career and will position her to effectively integrate these approaches for making novel and innovative
contributions to the field of chromatin biology.

## Key facts

- **NIH application ID:** 10105643
- **Project number:** 1K99GM140265-01
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Yadira M Soto-Feliciano
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2021-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105643

## Citation

> US National Institutes of Health, RePORTER application 10105643, Understanding mechanisms of transcriptional regulation by chromatin adaptor proteins (1K99GM140265-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10105643. Licensed CC0.

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