BEN domain protein Elba2 can functionally substitute for linker histone H1 in Drosophila in vivo.
Metazoan linker histones are essential for development and play crucial roles in organization of chromatin, modification of epigenetic states and regulation of genetic activity. Vertebrates express multiple linker histone H1 isoforms, which may function redundantly. In contrast, H1 isoforms are not present in Dipterans, including D. melanogaster, except for an embryo-specific, distantly related dBigH1. Here we show that Drosophila BEN domain protein Elba2, which is expressed in early embryos and was hypothesized to have insulator-specific functions, can compensate for the loss of H1 in vivo. Although the Elba2 gene is not essential, its mutation causes a disruption of normal internucleosomal spacing of chromatin and reduced nuclear compaction in syncytial embryos. Elba2 protein is distributed ubiquitously in polytene chromosomes and strongly colocalizes with H1. In H1-depleted animals, ectopic expression of Elba2 rescues the increased lethality and ameliorates abnormalities of chromosome architecture and heterochromatin functions. We also demonstrate that ectopic expression of BigH1 similarly complements the deficiency of H1 protein. Thus, in organisms that do not express redundant H1 isoforms, the structural and biological functions performed by canonical linker histones in later development, may be shared in early embryos by weakly homologous proteins, such as BigH1, or even unrelated, non-homologous proteins, such as Elba2.
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Na
N
Xu
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Xingwu
X
Lu
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Harsh
H
Kavi
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Alexander V
AV
Emelyanov
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Travis J
TJ
Bernardo
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Elena
E
Vershilova
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Arthur I
AI
Skoultchi
Albert Einstein College of Medicine, Department of Cell Biology, Bronx, NY 10461, USA.
Dmitry V
DV
Fyodorov
Curr Protoc Mol Biol. 2002 May;Chapter 21:Unit 21.7
18265309
Development. 2013 May;140(9):1892-902
23571214
Dev Cell. 2013 Sep 30;26(6):578-90
24055651
Mol Cell Biol. 2003 Jul;23(13):4559-72
12808097
G3 (Bethesda). 2015 Jan 27;5(4):677-87
25628309
Epigenetics Chromatin. 2014 Jul 28;7:16
25177369
Development. 2004 Mar;131(5):965-73
14973298
EMBO J. 2011 Jul 15;30(15):3120-33
21765394
Mol Cell. 2004 Dec 3;16(5):737-48
15574329
Genes Dev. 2009 Feb 15;23(4):452-65
19196654
EMBO J. 1994 Apr 15;13(8):1817-22
8168480
Science. 2013 Apr 5;340(6128):78-81
23559249
Crit Rev Eukaryot Gene Expr. 1997;7(3):215-30
9399071
J Biol Chem. 2016 Jul 15;291(29):15143-55
27226620
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12418-22
8901596
J Cell Sci. 1983 May;61:31-70
6411748
Genes Dev. 2004 Jan 15;18(2):170-83
14752009
Genes Dev. 2013 Mar 15;27(6):602-14
23468431
Int J Biochem Cell Biol. 1997 Dec;29(12):1463-6
9570139
Biol Chem. 2008 Apr;389(4):333-43
18208346
Biol Reprod. 2003 May;68(5):1569-76
12606334
Genes Dev. 2015 Jan 1;29(1):48-62
25561495
Elife. 2012 Dec 13;1:e00171
23240086
Science. 2007 Aug 24;317(5841):1087-90
17717186
Bioinformatics. 2008 Feb 15;24(4):458-61
18203771
Chromosome Res. 2006;14(1):17-25
16506093
Biochim Biophys Acta. 2016 Mar;1859(3):455-61
26455956