ISSN 10623604, Russian Journal of Developmental Biology, 2013, Vol. 44, No. 1, pp. 1–6. © Pleiades Publishing, Inc., 2013.
Original Russian Text © D.A. Kulikova, I.B. Mertsalov, O.B. Simonova, 2013, published in Ontogenez, 2013, Vol. 44, No. 1, pp. 3–9.
In the early 1970s, the group led by V.L. Buchman
identified previously unknown neurospecific gene
. This gene was cloned using a differential
screening of cDNA library derived from cerebral cortex
of 7–9dayold rats (Buchman et al., 1992). This gene
gene family. The family includes three
according to the nucleotide database
http://www.ncbi.nlm.nih.gov/nucleotide). The family
genesmediated proteins are characterized by similar
structure and high homology of amino acid sequences
of structural domains (Fig. 1). A unique domain 2/3
containing a nuclear localization signal, which is likely
necessary for protein penetration into cell nucleus, is in
the Nend domain. A domain homologous to known
DNAbinding sequences of Krüppeltype zinc fingers
and a stretch of negatively charged amino acids (puta
tive tarnscriptional activator) are in the central part of
the protein molecule (Buchman et al., 1992). In the
Cterminal end, there is the D4 domain, whose struc
ture appears as two “zinc fingers” of the PHDtype sit
uated one by one (Aasland et al., 1995) that participate
in the interaction with the modified H3 and H4 histone
proteins (Lange et al., 2008).
In spite of the fact that the general structure of the
family proteins is similar, their encoding genes vary in
structure, as well as in time and expression pattern.
Each gene is described separately below.
This gene was described by the groups led by
V.L. Buchman and T.G. Gabig. The first group cloned it
through the library screening of mouse, chicken, and
human after their hybridization with a probe of the gene
(Chestkov et al., 1996). Gabig’s group
revealed it trying to isolate the genes associated with an
apoptosis. They used interleukindependent mammal
Family Genes: Genomic Organization and Expression
D. A. Kulikova
, I. B. Mertsalov
, and O. B. Simonova
Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334 Russia
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia
Received September 17, 2010; in final form, November 28, 2010
—A family of closely related genes, named the
family, has been previously identified in mammals.
It comprises three genes encoding structurally related proteins. The hallmark of the family is D4 domain—a
doublepaired finger motif that consists of two tandemly arranged PHD finger domains. These genes are
expressed in various tissues and at various developmental stages. Two of those,
strictly neurospecific and their expression is developmentally regulated. Another gene,
ubiquitously expressed in all embryonic and adult tissues at the same levels.
family genes are evolutionary
conserved. Human, mouse, rat, and chicken
genes have been cloned. The only d4like gene was found in
the genome of nematode
. The sole member of
family was identified
also in the genome of
. However, d4 genes are not believed to be present in the genomes of
prokaryotes and yeast. This review describes genomic organization and expression of
family genes in ver
family genes, neurogenes, alternative splicing, transcription, specific gene expression, ubiqui
tously expressed genes
General scheme of D4 protein composition. Domain 2/3—domain 2/3, a novel domain that has no sequence similarity
to any other known protein sequences; NLS—nuclear localization signal; Krüppel—a single Krüppeltype zinc finger; acidic—
a stretch of negatively charged amino acids; d4domain—a cysteine/histidinerich region on the Cterminus common to all d4
proteins is a doublepaired finger motif that consists of two tandemly arranged PHD finger domains.