Linker histone H1.0 and JUNB Interaction Maintains Lineage-Specific and Age-Dependent Chromatin Architecture to Safeguard Cell Identity [CUT&Run]

ABSTRACT: Maintenance of differentiated cell identity is essential for tissue homeostasis and depends on active molecular mechanisms that reinforce cell fate stability. This thesis focuses on identifying the molecular factors involved in this maintenance system and defining how they function as barriers that oppose cell fate reprogramming and protect cellular identity. More broadly, this work addresses a fundamental question in biology: how differentiated cells actively preserve their identity while resisting inappropriate lineage programs, and how aging erodes these mechanisms, contributing to loss of cell identity in aged cells. In particular, this work examines how transcription factor barriers cooperate with chromatin regulators to maintain cell fate stability. In a previous study, JUNB was identified as a transcription factor barrier that restricts cell fate reprogramming through regulation of chromatin accessibility at both open and closed chromatin regions. Notably, transcription factors are not typically characterized for their ability to regulate closed chromatin states. Given that transcription factors frequently function in cooperation with other regulatory proteins, it was hypothesized that JUNB interacts with additional chromatin regulators to control chromatin accessibility more broadly. In this study, H1F0, a linker histone with chromatin-regulatory properties, was identified as a novel functional interactant of JUNB that acts as a barrier to cell fate reprogramming. Mechanistic investigation further demonstrated that JUNB and H1F0 cooperate at shared regulatory regions, including sites associated with the chromatin architectural regulator CTCF, to modulate chromatin accessibility. Through this coordinated action, engagement of lineage-reprogramming transcription factors with gene programs required for alternative fate activation was restricted, thereby preserving cell fate stability.

ORGANISM(S): Mus musculus

PROVIDER: GSE338102 | GEO | 2026/07/17

REPOSITORIES: GEO