Mapping of six somatic linker histone H1 variants in human breast cancer cells uncovers specific features of H1.2.
Seven linker histone H1 variants are present in human somatic cells with distinct prevalence across cell types. Despite being key structural components of chromatin, it is not known whether the different variants have specific roles in the regulation of nuclear processes or are differentially distributed throughout the genome. Using variant-specific antibodies to H1 and hemagglutinin (HA)-tagged recombinant H1 variants expressed in breast cancer cells, we have investigated the distribution of six H1 variants in promoters and genome-wide. H1 is depleted at promoters depending on its transcriptional status and differs between variants. Notably, H1.2 is less abundant than other variants at the transcription start sites of inactive genes, and promoters enriched in H1.2 are different from those enriched in other variants and tend to be repressed. Additionally, H1.2 is enriched at chromosomal domains characterized by low guanine-cytosine (GC) content and is associated with lamina-associated domains. Meanwhile, other variants are associated with higher GC content, CpG islands and gene-rich domains. For instance, H1.0 and H1X are enriched at gene-rich chromosomes, whereas H1.2 is depleted. In short, histone H1 is not uniformly distributed along the genome and there are differences between variants, H1.2 being the one showing the most specific pattern and strongest correlation with low gene expression.
Department of Molecular Genomics, Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Barcelona, E-08028 Spain, Research Programme on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, E-08003 Spain, Department of Genetic Engineering, Biotechnology, University of Dhaka, Dhaka-1000, Bangladesh, Centro de Investigación Príncipe Felipe, Valencia, E-46012 Spain and Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, E-08010 Spain.
Lluís
L
Millán-Ariño
Abul B M M K
AB
Islam
Andrea
A
Izquierdo-Bouldstridge
Regina
R
Mayor
Jean-Michel
JM
Terme
Neus
N
Luque
Mónica
M
Sancho
Núria
N
López-Bigas
Albert
A
Jordan
D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006657:Histones / Q000032:analysis* / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D006657:Histones