Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The roles of Rett Syndrome protein MECP2 at gene regulatory elements

Award Number: R01MH142417
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/05/2026
PERIOD OF PERFORMANCE END DATE: 12/31/2030

Group Awards By:

View Award Description

The roles of Rett Syndrome protein MECP2 at gene regulatory elements - Project Summary: Rett Syndrome (RTT) is a progressive neurological disorder characterized by severe cognitive and motor impairments caused primarily by mutations in MECP2. The molecular mechanisms by which disruption of MECP2 gives rise to RTT remain unclear. MECP2 is known to bind to methylated DNA in the brain, regulating the expression of neuronal genes. However, previous studies have shown complex patterns of gene dysregulation in RTT that challenge this model, such that only a subset of genes appear to be regulated by MECP2 binding to DNA methylation. We recently discovered that MECP2 preferentially binds to specific gene enhancers that we named MECP2-Binding Hotspots (MBHs). Surprisingly, MECP2 binds to these MBHs independently of DNA methylation, contrasting with its well-established role in binding methylated DNA. At MBHs, MECP2 appears to act as a repressor of enhancer activity. Importantly, over 60% of genes derepressed upon MECP2 deletion are associated with MBHs, suggesting that MBHs might be a major mechanism by which MECP2 controls genes. Preliminary analyses indicate that MBHs, but not MECP2 bound to methylated sites across the genome, are bound by histone deacetylase-containing nuclear receptor co- repressor (NCOR) complex, suggesting that MBHs may repress enhancer activity by recruiting the NCOR complex to enhancers. Taken together, our findings indicate a previously uncharacterized mechanism of transcriptional regulation by MECP2. Moreover, these results implicate dysregulation of specific enhancers as a possible mechanism underlying RTT. To gain insights into how MECP2 regulates genes and how dysregulation of MECP2 leads to RTT, we propose to (1) define the interaction between MECP2 and MBHs, and (2) elucidate the molecular mechanisms by which MBHs repress enhancers. This work has significant implications for understanding the molecular basis of MECP2 function and the complex gene dysregulation observed in RTT and will uncover new therapeutic targets and strategies for treating RTT.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $641,828 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	1	3/3/2026	NEW	$641,828
														Subtotal = $641,828

Grand Total All Awards = $641,828

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The roles of Rett Syndrome protein MECP2 at gene regulatory elements

Award Number: R01MH142417

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/05/2026

PERIOD OF PERFORMANCE END DATE: 12/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer