Table 3.
Summary of properties of mice and ESCs with altered H1 expression
| H1 manipulationa | H1/nucleosome ratiob | Phenotype | References | |
|---|---|---|---|---|
| In mice | ||||
|
| ||||
| H1 OE | H10 | N/D | Normal (10–20 fold increase in H10 mRNA, N/C in H10 protein) | [198] |
|
| ||||
| Single H1 KOs | H10−/− | N/C (adult liver: 0.68) | Normal | [103] |
| Decreased dendritic cell production; reduced response to vaccination with antigens | [118] | |||
| H1a−/− | N/C (male germ cells: 0.73) | Normal | [107, 135] | |
| H1c−/− | N/C | Normal | [108] | |
| Increased resistance to x-ray induced apoptosis in thymocytes and intestine | [120] | |||
| RD (PN56 retina: WT 1.25/KO 0.99) | Normal retina | [117] | ||
| H1d−/− | N/C | Normal | [108] | |
| H1e−/− | N/C | Normal | [108] | |
| H1oo−/− | N/D | Normal | [98] | |
| Or homeostasis | [99] | |||
| H1t−/− | N/C (male germ cells: 0.68) | Normal | [132–134] | |
| H1T2−/− | N/D | Abnormal sperms and male infertility | [28] | |
|
| ||||
| Double H1 KOs | H10−/−H1c−/− | N/C (adult liver: 0.71) | Normal | [108] |
| H10−/−H1d−/− | N/C (adult liver: 0.71) | Normal | [108] | |
| H10−/−H1e−/− | N/C (adult liver: 0.76) | Normal | [108] | |
| H1c−/−H1e−/− | N/C (adult liver: 0.72) | Mild growth retardation | [13] | |
| RD (retina) | Abnormal rod photoreceptor packing | [117] | ||
| H1a−/−H1t−/− | RD (male germ cells: WT 0.78/KO 0.59) | Normal | [135] | |
|
| ||||
| Triple H1 KOs | H1c−/−H1e−/−H10−/− | RD (adult liver: WT 0.79/KO 0.64) | Growth retardation; lower birth rate; small thymus | [13] |
| RD (retina) | Abnormal rod photoreceptor packing | [117] | ||
| H1c−/−H1d−/−H1e−/− | RD (midgestation embryo: WT 0.74/KO 0.40) | Embryonic lethality by E11.5 | [13] | |
|
| ||||
| Other compound H1 KOs with multiple H1 null alleles | H1c−/−H1d+/−H1e−/− | RD (thymus:WT0.83/KO 0.41) | Low birth rate; severe growth retardation | [13] |
| H1c−/−H1d+/−H1e−/−H10−/− | N/D | Low birth rate; neonatal lethality | [13] | |
| H1c−/−H1d−/−H1e−/−H10−/− | N/D | Embryonic lethality | [13] | |
|
| ||||
| In ESCs | ||||
|
| ||||
| Single H1 KOs (mouse) | H10−/− | N/D | Normal ESC differentiation | # |
|
| ||||
| H1c−/− | RD (WT 0.45/KO 0.38) | Normal cell morphology and proliferation; normal ESC differentiation and teratoma formation; specific expression changes of Hox genes | [154] | |
| H1d−/− | RD (WT 0.45/KO 0.35) | [154] | ||
| H1e−/− | RD (WT 0.45/KO 0.35) | [154] | ||
|
| ||||
| Triple H1 KO (mouse) | H1c−/−H1d−/−H1e−/− | RD (ESCs: WT 0.46/KO 0.25) | Reduced chromatin compaction; specific changes in gene expression and DNA methylation | [153] |
| Chromocenter clustering and de-repression of major satellite repeats | [109] | |||
| Enhanced DNA damage response | [199] | |||
| Decreased chromatin flexibility in gene rich TAD | [163] | |||
| RD (EBs: WT 0.62/KO 0.36) | ESCs more resistant to spontaneous differentiation; impaired EB and neural differentiation | [16] | ||
| [16] | ||||
| Dysregulated in specification of mesendoderm and neuroectoderm | [105] | |||
|
| ||||
| H1 KD (human) | H10 | N/D | Lack of induction of a few differentiation associated genes | [106] |
a
OE, overexpression; KO, knockout; KD, knockdown.
b
N/C, no change; RD, reduced; N/D, not determined; WT, wildtype.
#
Pan, Zhang, Fan unpublished observation.