eprintid: 37069
rev_number: 23
eprint_status: archive
userid: 8929
dir: disk0/00/03/70/69
datestamp: 2025-08-07 13:03:57
lastmod: 2025-08-07 13:04:02
status_changed: 2025-08-07 13:03:57
type: doctoralThesis
metadata_visibility: show
creators_name: Neu, Marco
title: Biophysical Characterization of TRIM24's Role in Cardiomyocytes
subjects: ddc-530
subjects: ddc-570
subjects: ddc-610
divisions: i-130700
adv_faculty: af-13
cterms_swd: TRIM24
cterms_swd: Cardiomyocytes
cterms_swd: Chromatin
abstract: Cardiomyocyte function and survival rely on tightly controlled quality control systems that safeguard both nuclear integrity and cellular homeostasis. While the E3 ubiquitin ligase TRIM24 has been extensively studied in cancer and neurodegeneration, its role in the heart remained unclear. This dissertation presents a comprehensive characterization of TRIM24 in cardiomyocytes through genome-wide sequencing, targeted biochemical assays, and biophysical imaging techniques. These approaches revealed that TRIM24 modulates chromatin architecture and  transcriptional regulation, thereby shaping gene expression programs relevant to cardiac function. Among these, TRIM24 was found to suppress inflammatory signaling in cardiomyocytes, extending its known immunomodulatory role into the cardiac context for the first time. Furthermore, the study identifies a novel function of TRIM24 in calcium handling and excitation-contraction coupling. By integrating super-resolution microscopy, functional calcium imaging, and contractility assays, the study demonstrates that TRIM24-dependent structural remodeling of calcium channel organization is associated with altered calcium cycling and measurable changes in cardiomyocyte contraction. Together, this work positions TRIM24 as a multifunctional regulator in cardiomyocytes, linking chromatinlevel control to physiological signaling pathways. These insights advance our understanding of cardiac proteostasis and may offer new therapeutic entry points for cardiovascular disease.
date: 2026
id_scheme: DOI
id_number: 10.11588/heidok.00037069
own_urn: urn:nbn:de:bsz:16-heidok-370694
date_accepted: 2025-07-23
advisor: HASH(0x55602a799778)
language: eng
bibsort: NEUMARCOBIOPHYSICA
full_text_status: restricted
place_of_pub: Heidelberg
citation:   Neu, Marco  (2026) Biophysical Characterization of TRIM24's Role in Cardiomyocytes.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/37069/1/Biophysical%20Characterization%20of%20TRIM24%27s%20Role%20in%20Cardiomyocytes_PDFA.pdf