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Comment |
SSR 2010 Abstract 34. Metastasis Tumor Antigen 2 (MTA2) Is Involved in Genomic
Imprinting During Mouse Preimplantation Embryogenesis. Pengpeng Ma, Shu
Lin, Marisa S. Bartolomei, and Richard M. Schultz. University of Pennsylvania,
Philadelphia, PA, USA
The epigenetic mechanisms involved in establishing and maintaining genomic
imprinting are steadily being unmasked. The nucleosome remodeling and histone
deacetylation (NuRD) complex is implicated in regulating DNA methylation and
expression of the maternally-expressed H19 gene in preimplantation mouse embryos.
The NuRD complex in mammalian cells is composed of at least 7 polypeptides. Four
of the components, HDAC1 and HDAC2 and two histone-binding proteins (RBBP4/
RbAp46, RBBP7/RbAp48), form a deacetylase complex that is also found in the
Sin3A histone deacetylase complex. The other three components, CHD4 (Mi-2beta),
MBD3, and MTA, however, appear to be unique to the NuRD complex. CHD4 is an
ATP-dependent nucleosome-remodeling enzyme. Although mammalian MBD3 does
not bind to methylated DNA, when NuRD binds MBD2, the resulting NuRD
complex becomes an integral component of the MeCP1 complex that can bind to
methylated DNA, thereby leading to histone deacetylation of DNA methylated
nucleosomes. MTA proteins, which are the last characterized proteins of the NuRD
complex, are encoded by three genes, and It appears that only one MTA family
member is found within a given NuRD complex. To dissect further the function of the
NuRD complex in genomic imprinting we employed an RNAi strategy to deplete the
NuRD complex components Metastasis Tumor Antigen (MTA) 1, 2, and 3). We find
that Mta2 is the only zygotically expressed Mta gene prior to the blastocyst stage and
that RNAi-mediated knockdown of Mta2 transcript leads to biallelic H19 expression
and loss of DNA methylation in the imprinting control region (ICR) in blastocysts. In
addition, biallelic expression of the paternally-expressed Peg3 gene, but not Snrpn, is
also observed in blastocysts following Mta2 knockdown. Loss of MTA2 protein does
not result in a decrease in abundance of other NuRD components, including MBD2
and 3, HDAC1 and 2, and CHD4. No reduction in the amount of MTA1 or MTA3
was observed following targeting of their mRNAs, precluding any insight into the
role of these two genes in genomic imprinting. Taken together, our results support a
role of MTA2 within the NuRD complex in genomic imprinting.
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