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The pioneer activity of transcription factors allows for opening of inaccessible regulatory elements and has been extensively studied in the context of cellular differentiation and reprogramming. In contrast, the function of pioneer activity in self-renewing cell divisions and across the cell cycle is poorly understood. Here we assessed the interplay between OCT4 and SOX2 in controlling chromatin accessibility of mouse embryonic stem cells. We found that OCT4 and SOX2 operate in a largely independent manner even at co-occupied sites, and that their cooperative binding is mostly mediated indirectly through regulation of chromatin accessibility. Controlled protein degradation strategies revealed that the uninterrupted presence of OCT4 is required for post-mitotic re-establishment and interphase maintenance of chromatin accessibility, and that highly OCT4-bound enhancers are particularly vulnerable to transient loss of OCT4 expression. Our study sheds light on the constant pioneer activity required to maintain the dynamic pluripotency regulatory landscape in an accessible state.
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Remodeling of chromatin accessibility is necessary for successful reprogramming of fibroblasts to neurons. However, it is still not fully known which transcription factors can induce a neuronal chroma...
Genomic events including gene regulation and chromatin status are controlled by transcription factors. Here we report that the Hsp90 molecular chaperone broadly regulates the transcription factor prot...
During latent infections with herpes simplex virus 1 (HSV-1), viral transcription is restricted and the genomes are mostly maintained in silenced chromatin, whereas in lytically infected cells all vir...
Chromatin accessibility to protein factors is critical for genome activities. However, the dynamic properties of chromatin higher-order structures that regulate its accessibility are poorly understood...
Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical pro...
Oxidative stress and inflammation are cardiovascular risk factors in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). Nuclear transcription factors play roles in th...
Epigenetic mechanisms have been implicated in the pathogenesis of food allergy. The investigators previously demonstrated that tolerance acquisition in children with Immunoglobulin E- (IgE...
The purpose of this study is to evaluate the efficiency and the safe use of a new medical device to improve the oral accessibility of disabled people during the oral-dental examination.
The main objective of this project is not only a better understanding of the human leukemic disease but also to find new anti-leukemic or improve existing ones. This study has, the followi...
Ewing sarcoma is characterized by genomic rearrangements resulting in over-expression of ets family transcription factors driving tumor progression. TK216 is designed to inhibit this effec...
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
A family of histone acetyltransferases that is structurally-related to CREB-BINDING PROTEIN and to E1A-ASSOCIATED P300 PROTEIN. They function as transcriptional coactivators by bridging between DNA-binding TRANSCRIPTION FACTORS and the basal transcription machinery. They also modify transcription factors and CHROMATIN through ACETYLATION.
Basic helix-loop-helix (bHLH) domain-containing proteins that play important roles in CIRCADIAN RHYTHM regulation. They combine with CLOCK PROTEINS to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation.
The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA.
A subclass of SOX transcription factors that are expressed in neuronal tissue where they may play a role in the regulation of CELL DIFFERENTIATION. Members of this subclass are generally considered to be transcriptional activators.
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