Within 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 oncoprotein SET is a critical determinant for the levels of histone acetylation within enhancers. We disclose that a condition in which SET is accumulated, the severe Schinzel-Giedion Syndrome (SGS), is 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 SGS and possibly other the SET-related disorders in humans.

Zaghi, M., Banfi, F., Massimino, L., Volpin, M., Bellini, E., Brusco, S., et al. (2023). Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition. NATURE COMMUNICATIONS, 14(1) [10.1038/s41467-023-39043-x].

Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition

Massimino, Luca;Brusco, Simone;Barone, Cristiana;D'Aliberti, Deborah;Spinelli, Silvia;Mologni, Luca;Azzoni, Emanuele;Piazza, Rocco;
2023

Abstract

Within 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 oncoprotein SET is a critical determinant for the levels of histone acetylation within enhancers. We disclose that a condition in which SET is accumulated, the severe Schinzel-Giedion Syndrome (SGS), is 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 SGS and possibly other the SET-related disorders in humans.
Articolo in rivista - Articolo scientifico
cell differentiation; genetics; chromatin; SET; Schinzel-Gedion syndrome; gene regulation
English
3-giu-2023
2023
14
1
3212
open
Zaghi, M., Banfi, F., Massimino, L., Volpin, M., Bellini, E., Brusco, S., et al. (2023). Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition. NATURE COMMUNICATIONS, 14(1) [10.1038/s41467-023-39043-x].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/419667
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