| linker histone H1 and H5 family | |||||||||||
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| Identifiers | |||||||||||
| Symbol | Linker_histone | ||||||||||
| Pfam | PF00538 | ||||||||||
| InterPro | IPR005818 | ||||||||||
| SMART | SM00526 | ||||||||||
| SCOP2 | 1hst / SCOPe / SUPFAM | ||||||||||
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Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species.
Metazoan H1 proteins feature a central globular "winged helix" domain and long C- and short N-terminal tails. H1 is involved with the packing of the "beads on a string" sub-structures into a high order structure, whose details have not yet been solved. [1] H1 found in protists and bacteria, otherwise known as nucleoproteins HC1 and HC2 (Pfam PF07432, PF07382), lack the central domain and the N-terminal tail. [2]
H1 is less conserved than core histones. The globular domain is the most conserved part of H1. [3]
Unlike the other histones, H1 does not make up the nucleosome "bead". Instead, it sits on top of the structure, keeping in place the DNA that has wrapped around the nucleosome. H1 is present in half the amount of the other four histones, which contribute two molecules to each nucleosome bead. In addition to binding to the nucleosome, the H1 protein binds to the "linker DNA" (approximately 20-80 nucleotides in length) region between nucleosomes, helping stabilize the zig-zagged 30 nm chromatin fiber. [4] Much has been learned about histone H1 from studies on purified chromatin fibers. Ionic extraction of linker histones from native or reconstituted chromatin promotes its unfolding under hypotonic conditions from fibers of 30 nm width to beads-on-a-string nucleosome arrays. [5] [6] [7]
It is uncertain whether H1 promotes a solenoid-like chromatin fiber, in which exposed linker DNA is shortened, or whether it merely promotes a change in the angle of adjacent nucleosomes, without affecting linker length [8] However, linker histones have been demonstrated to drive the compaction of chromatin fibres that had been reconstituted in vitro using synthetic DNA arrays of the strong '601' nucleosome positioning element. [9] Nuclease digestion and DNA footprinting experiments suggest that the globular domain of histone H1 localizes near the nucleosome dyad, where it protects approximately 15-30 base pairs of additional DNA. [10] [11] [12] [13] In addition, experiments on reconstituted chromatin reveal a characteristic stem motif at the dyad in the presence of H1. [14] Despite gaps in our understanding, a general model has emerged wherein H1's globular domain closes the nucleosome by crosslinking incoming and outgoing DNA, while the tail binds to linker DNA and neutralizes its negative charge. [8] [12]
Many experiments addressing H1 function have been performed on purified, processed chromatin under low-salt conditions, but H1's role in vivo is less certain. Cellular studies have shown that overexpression of H1 can cause aberrant nuclear morphology and chromatin structure, and that H1 can serve as both a positive and negative regulator of transcription, depending on the gene. [15] [16] [17] In Xenopus egg extracts, linker histone depletion causes ~2-fold lengthwise extension of mitotic chromosomes, while overexpression causes chromosomes to hypercompact into an inseparable mass. [18] [19] Complete knockout of H1 in vivo has not been achieved in multicellular organisms due to the existence of multiple isoforms that may be present in several gene clusters, but various linker histone isoforms have been depleted to varying degrees in Tetrahymena, C. elegans, Arabidopsis, fruit fly, and mouse, resulting in various organism-specific defects in nuclear morphology, chromatin structure, DNA methylation, and/or specific gene expression. [20] [21] [22]
While most histone H1 in the nucleus is bound to chromatin, H1 molecules shuttle between chromatin regions at a fairly high rate. [23] [24]
It is difficult to understand how such a dynamic protein could be a structural component of chromatin, but it has been suggested that the steady-state equilibrium within the nucleus still strongly favors association between H1 and chromatin, meaning that despite its dynamics, the vast majority of H1 at any given timepoint is chromatin bound. [25] H1 compacts and stabilizes DNA under force and during chromatin assembly, which suggests that dynamic binding of H1 may provide protection for DNA in situations where nucleosomes need to be removed. [26]
Cytoplasmic factors appear to be necessary for the dynamic exchange of histone H1 on chromatin, but these have yet to be specifically identified. [27] H1 dynamics may be mediated to some degree by O-glycosylation and phosphorylation. O-glycosylation of H1 may promote chromatin condensation and compaction. Phosphorylation during interphase has been shown to decrease H1 affinity for chromatin and may promote chromatin decondensation and active transcription. However, during mitosis phosphorylation has been shown to increase the affinity of H1 for chromosomes and therefore promote mitotic chromosome condensation. [19]
The H1 family in animals includes multiple H1 isoforms that can be expressed in different or overlapping tissues and developmental stages within a single organism. The reason for these multiple isoforms remains unclear, but both their evolutionary conservation from sea urchin to humans as well as significant differences in their amino acid sequences suggest that they are not functionally equivalent. [28] [29] [3] One isoform is histone H5, which is only found in avian erythrocytes, which are unlike mammalian erythrocytes in that they have nuclei. Another isoform is the oocyte/zygotic H1M isoform (also known as B4 or H1foo), found in sea urchins, frogs, mice, and humans, which is replaced in the embryo by somatic isoforms H1A-E, and H10 which resembles H5. [3] [30] [31] [32] Despite having more negative charges than somatic isoforms, H1M binds with higher affinity to mitotic chromosomes in Xenopus egg extracts. [19]
Like other histones, the histone H1 family is extensively post-translationally modified (PTMs). This includes serine and threonine phosphorylation, lysine acetylation, lysine methylation and ubiquitination. [33] These PTMs serve a variety of functions but are less well studied than the PTMs of other histones.
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4.
In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.
Histone H2B is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and long N-terminal and C-terminal tails, H2B is involved with the structure of the nucleosomes.
The family of heterochromatin protein 1 (HP1) consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcriptional activation, regulation of binding of cohesion complexes to centromeres, sequestration of genes to the nuclear periphery, transcriptional arrest, maintenance of heterochromatin integrity, gene repression at the single nucleosome level, gene repression by heterochromatization of euchromatin, and DNA repair. HP1 proteins are fundamental units of heterochromatin packaging that are enriched at the centromeres and telomeres of nearly all eukaryotic chromosomes with the notable exception of budding yeast, in which a yeast-specific silencing complex of SIR proteins serve a similar function. Members of the HP1 family are characterized by an N-terminal chromodomain and a C-terminal chromoshadow domain, separated by a hinge region. HP1 is also found at some euchromatic sites, where its binding can correlate with either gene repression or gene activation. HP1 was originally discovered by Tharappel C James and Sarah Elgin in 1986 as a factor in the phenomenon known as position effect variegation in Drosophila melanogaster.
The solenoid structure of chromatin is a model for the structure of the 30 nm fibre. It is a secondary chromatin structure which helps to package eukaryotic DNA into the nucleus.
Histone H3.1 is a protein that in humans is encoded by the HIST1H3B gene.
Core histone macro-H2A.1 is a protein that in humans is encoded by the H2AFY gene.
Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the HMGN1 gene.
Histone H1.1 is a protein that in humans is encoded by the HIST1H1A gene.
Histone H3.1 is a protein in humans that is encoded by the H3C1 gene.
Histone H1.4 is a protein that in humans is encoded by the HIST1H1E gene.
Histone H3.1 is a protein that in humans is encoded by the HIST1H3F gene.
Histone H1.3 is a protein that in humans is encoded by the HIST1H1D gene.
Histone H1x is a protein that in humans is encoded by the H1FX gene.
Histone H2A.J is a protein that in humans is encoded by the H2AFJ gene.
Histone H2A-Bbd type 1 also known as H2A Barr body-deficient is a histone protein variant that in humans is encoded by the H2AFB1 gene.
Histone H2A-Bbd type 2/3 also known as H2A Barr body-deficient is a histone protein that in humans is encoded by the H2AFB2 gene.
In molecular biology, the linker histone H1 is a protein family forming a critical component of eukaryotic chromatin. H1 histones bind to the linker DNA exiting from the nucleosome core particle, while the core histones form the octamer core of the nucleosome around which the DNA is wrapped.