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Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition
- Source :
- bioRxiv
- Publication Year :
- 2022
- Publisher :
- Cold Spring Harbor Laboratory, 2022.
-
Abstract
- SUMMARYWithin the chromatin, distal elements interact with promoters to regulate specific transcriptional programs. Histone acetylation, interfering with the net charges of the nucleosomes, is a key player in this regulation. Here, we report that the onco-protein SET is a critical determinant for the levels of histone acetylation within enhancers. We disclose that conditions in which SET is accumulated, including the severe Schinzel-Giedion Syndrome (SGS), are characterized by a failure in the usage of the distal regulatory regions typically employed during fate commitment. This is accompanied by the usage of alternative enhancers leading to a massive rewiring of the distal control of the gene transcription. This represents a (mal)adaptive mechanism that, on one side, allows to achieve a certain degree of differentiation, while on the other affects the fine and corrected maturation of the cells. Thus, we propose the differential in cis-regulation as a contributing factor to the pathological basis of the SET-related disorders in humans, including SGS, neurodevelopmental disorders, myeloproliferative diseases, and cancer.
- Subjects :
- cell differentiation
Schinzel-Gedion syndrome
chromatin
genetic
gene regulation
SET
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- bioRxiv
- Accession number :
- edsair.doi.dedup.....51151bb71d99ec37c842c60fd25abfcd