Towards understanding the Regulation of Histone H1 Somatic Subtypes with OMICs
Ponte Marull, Immaculada (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Andrés Nieto, Marta (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Jordan, Albert (Molecular Biology Institute of Barcelona (IBMB-CSIC))
Roque Córdova, Alicia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Universitat Autònoma de Barcelona. SGR-Grup de Recerca d'Estudi de Proteïnes Autoagregatives

Data:	2021
Descripció:	18 pàg.
Resum:	Histone H1 is involved in the regulation of chromatin higher-order structure and compaction. In humans, histone H1 is a multigene family with seven subtypes differentially expressed in somatic cells. Which are the regulatory mechanisms that determine the variability of the H1 complement is a long-standing biological question regarding histone H1. We have used a new approach based on the integration of OMICs data to address this issue. We have examined the 3D-chromatin structure, the binding of transcription factors (TFs), and the expression of somatic H1 genes in human cell lines, using data from public repositories, such as ENCODE. Analysis of Hi-C, ChIP-seq, and RNA-seq data, have revealed that transcriptional control has a greater impact on H1 regulation than previously thought. Somatic H1 genes located in topologically associated domains (TADs) show higher expression than in boundary regions. H1 genes are targeted by a variable number of transcription factors including cell cycle-related TFs, and tissue-specific TFs, suggesting a fine-tuned, subtype-specific transcriptional control. We describe, for the first time, that all H1 somatic subtypes are under transcriptional co-regulation. The replication-independent subtypes, which are encoded in different chromosomes isolated from other histone genes, are also co-regulated with the rest of the somatic H1 genes, indicating that transcriptional co-regulation extends beyond the histone cluster. Transcriptional control and transcriptional co-regulation explain, at least in part, the variability of H1 complement, the fluctuations of H1 subtypes during development, and also the compensatory effects observed, in model systems, after perturbation of one or more H1 subtypes.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Chromatin compartments ; Co-regulation ; Subtype functional differentiation ; Topologically associated domains (TADs) ; Transcription factors ; Cell Line ; Promoter Regions, Genetic ; Humans ; Chromosome Mapping ; Gene Expression Profiling ; Genomics/methods ; Histones/chemistry ; Transcription Factors/metabolism ; Chromatin/genetics ; Protein Binding ; Proteomics/methods
Publicat a:	Journal of Molecular Biology, Vol. 433 Núm. 2 (2021) , p. 166734, ISSN 1089-8638

DOI: 10.1016/j.jmb.2020.166734
PMID: 33279581

Postprint 69 p, 3.7 MB

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