ABSTRACT
H1 linker histones are the most abundant chromatin-binding proteins1. In vitro studies indicate that their association with chromatin determines nucleosome spacing and enables arrays of nucleosomes to fold into more compact chromatin structures. However, the in vivo roles of H1 are poorly understood2. Here we show that the local density of H1 controls the balance of repressive and active chromatin domains by promoting genomic compaction. We generated a conditional triple-H1-knockout mouse strain and depleted H1 in haematopoietic cells. H1 depletion in T cells leads to de-repression of T cell activation genes, a process that mimics normal T cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T cells reveals that H1-mediated chromatin compaction occurs primarily in regions of the genome containing higher than average levels of H1: the chromosome conformation capture (Hi-C) B compartment and regions of the Hi-C A compartment marked by PRC2. Reduction of H1 stoichiometry leads to decreased H3K27 methylation, increased H3K36 methylation, B-to-A-compartment shifting and an increase in interaction frequency between compartments. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. Our results establish H1 as a critical regulator of gene silencing through localized control of chromatin compaction, 3D genome organization and the epigenetic landscape.
Subject(s)
Chromatin Assembly and Disassembly , Chromatin/genetics , Epigenesis, Genetic , Histones/metabolism , Animals , CD8-Positive T-Lymphocytes/metabolism , Cell Differentiation/genetics , Chromatin/chemistry , Chromatin/metabolism , Enhancer of Zeste Homolog 2 Protein/metabolism , Female , Gene Silencing , Histones/chemistry , Lymphocyte Activation/genetics , Male , Methylation , Mice , Mice, KnockoutABSTRACT
Although chemical interactions play an essential role in lizard social behavior, the chemical composition of the femoral gland secretions that many lizards use for communication is known for only a few species, mainly European Lacertids. The tegu lizard, Salvator merianae, is the only species of the Teiidae family for which there is available information on lipids in femoral secretions, but only for captive bred males from Argentina. Here, based on mass spectra obtained by GC-MS, we found 69 lipophilic compounds in femoral gland secretions of wild males S. merianae from Brazil, including cholesterol and high amounts of saturated fatty acids (mainly hexadecanoic and octadecanoic). We found contrasting differences between wild and captive-bred males, which lack cholesterol but present high amount of 9,12-octadecadienoic acid. These within-species differences between wild and captive lizards strongly suggest the important influence of different diets on the chemical composition of the femoral gland secretion and suggest caution when interpreting results from captive animals, even in the same species.
Subject(s)
Biological Transport/genetics , Lipids/chemistry , Lizards/genetics , Animals , Brazil , Fatty Acids/genetics , Fatty Acids/metabolism , Lipids/genetics , MaleABSTRACT
Although chemical interactions play an essential role in lizard social behavior, the chemical composition of the femoral gland secretions that many lizards use for communication is known for only a few species, mainly European Lacertids. The tegu lizard, Salvator merianae, is the only species of the Teiidae family for which there is available information on lipids in femoral secretions, but only for captive bred males from Argentina. Here, based on mass spectra obtained by GC-MS, we found 69 lipophilic compounds in femoral gland secretions of wild males S. merianae from Brazil, including cholesterol and high amounts of saturated fatty acids (mainly hexadecanoic and octadecanoic). We found contrasting differences between wild and captive-bred males, which lack cholesterol but present high amount of 9,12-octadecadienoic acid. These within-species differences between wild and captive lizards strongly suggest the important influence of different diets on the chemical composition of the femoral gland secretion and suggest caution when interpreting results from captive animals, even in the same species.
ABSTRACT
Although chemical interactions play an essential role in lizard social behavior, the chemical composition of the femoral gland secretions that many lizards use for communication is known for only a few species, mainly European Lacertids. The tegu lizard, Salvator merianae, is the only species of the Teiidae family for which there is available information on lipids in femoral secretions, but only for captive bred males from Argentina. Here, based on mass spectra obtained by GC-MS, we found 69 lipophilic compounds in femoral gland secretions of wild males S. merianae from Brazil, including cholesterol and high amounts of saturated fatty acids (mainly hexadecanoic and octadecanoic). We found contrasting differences between wild and captive-bred males, which lack cholesterol but present high amount of 9,12-octadecadienoic acid. These within-species differences between wild and captive lizards strongly suggest the important influence of different diets on the chemical composition of the femoral gland secretion and suggest caution when interpreting results from captive animals, even in the same species.
