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1.
EMBO J ; 39(22): e105098, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-32960481

RESUMEN

Chromatin remodeling complexes have functions in transcriptional regulation and chromosome maintenance, but it is mostly unknown how the function of these normally ubiquitous complexes is specified in the cellular context. Here, we describe that the evolutionary conserved long non-coding RNA linc-MYH regulates the composition of the INO80 chromatin remodeler complex in muscle stem cells and prevents interaction with WDR5 and the transcription factor YY1. Linc-MYH acts as a selective molecular switch in trans that governs the pro-proliferative function of the ubiquitous INO80 complex but does not affect its role in maintaining genomic stability. The molecular switch is essential for restricting generation of quiescent MuSCs and proliferation of myoblasts in homeostasis and regeneration. Since linc-MYH is expressed in proliferating myoblasts but not in quiescent MuSCs, we reason that the extent of myoblast proliferation has decisive effects on the size of the quiescent MuSC pool.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de Unión al ADN/metabolismo , Hipertrofia/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , ARN Largo no Codificante/metabolismo , ATPasas Asociadas con Actividades Celulares Diversas/genética , Animales , Proliferación Celular , Cromatina , ADN Glicosilasas/genética , Proteínas de Unión al ADN/genética , Epigenómica , Regulación Enzimológica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Noqueados , Músculo Esquelético/citología , Mioblastos/citología , ARN Largo no Codificante/genética , ARN no Traducido , Regeneración/fisiología , Transcriptoma , Factor de Transcripción YY1/genética
2.
Transcription ; 11(1): 3-18, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31856658

RESUMEN

Nascent transcription assays, such as global run-on sequencing (GRO-seq) and precision run-on sequencing (PRO-seq), have uncovered a myriad of unstable RNAs being actively produced from numerous sites genome-wide. These transcripts provide a more complete and immediate picture of the impact of regulatory events. Transcription factors recruit RNA polymerase II, effectively initiating the process of transcription; repressors inhibit polymerase recruitment. Efficiency of recruitment is dictated by sequence elements in and around the RNA polymerase loading zone. A combination of sequence elements and RNA binding proteins subsequently influence the ultimate stability of the resulting transcript. Some of these transcripts are capable of providing feedback on the process, influencing subsequent transcription. By monitoring RNA polymerase activity, nascent assays provide insights into every step of the regulated process of transcription.


Asunto(s)
ARN/genética , Transcripción Genética/genética , Animales , Elementos de Facilitación Genéticos/genética , Humanos , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
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