Page 57 - Mouse Molecular Genetics

Full Abstracts
Program number is above title. Author in bold is the presenter.
An evaluation of parent-of-origin bias and individual variation in the midgestation mouse placenta. Elizabeth H Finn
Cheryl Smith, Arend Sidow, Julie C Baker. Department of Genetics, Stanford University, Stanford, CA.
The placenta provides a unique epigenetic landscape characterized by increased flexibility of epigenetic marks and remarkable
environmental sensitivity. We examined genomic imprinting and parent-of-origin bias in the mouse placenta using 3-end
Sequencing for Expression Quantification (3SEQ) of F1 interspecies hybrid tissues. We sequenced 23 individual midgestation
placentas, five late stage placentas and two yolk sac samples, and used differential expression of SNPs to determine whether
transcripts were preferentially generated from the maternal or paternal allele. We found 103 genes that show significant parent-
of-origin bias, of which 78 were novel candidates for imprinting and 25 were previously identified imprinted genes. Most of our
novel candidates show a strong maternal bias which, using multiple models for maternal contamination, we demonstrate is not
due to decidual contamination. We also show evidence of paternally biased expression of Xist leading to maternally biased
expression of most X chromosome loci, with three regions escaping this inactivation. Finally, sequencing individual placentas
allowed us to reveal a surprising expression similarity between littermates. These data demonstrate the complexity and dynamic
nature of epigenetic pathways in the placenta.
Gene silencing by the
in vivo
dynamics of Polycomb repressive complex PRC1. Kyoichi Isono
Haruhiko Koseki
. 1)
RIKEN RCAI, Yokohama, Japan; 2) JST, PREST, Yokohama, Japan.
During embryogenesis, expressional change of genes and maintenance of its status give rise to cellular identity. Polycomb
group (PcG) proteins mediate heritable but reversible silencing of developmental regulatory genes by modifying their chromatin
configuration. Accumulating evidence documents a role for PcG proteins in regulating higher order chromatin structures, likely
by forming large complexes. However, little is still known about the molecular mechanisms underlying PcG-mediated gene
silencing. In this study using imaging approaches of mouse primary cells, we show that (1) Polycomb repressive complexes-1
PRC1) including Ring1b, Mel18, Cbx2, Phc2 and so on cluster at canonical PcG target genes, which are visualized as nuclear
foci such as a so-called PcG body in
; (2)
the PRC1-clustering depends on the head-to-tail polymerization property of
the SAM domain of Phc2 and also was accompanied by recruitment of Ring1b, chromatin condensation, and gene silencing. Our
findings suggest a new model in which SAM polymerization of Phc2 modulates the structural organization of PRC1 to enable
robust yet reversible PcG-mediated gene repression during development and in cell fate decision-making.
Concerted alterations of promoter-enhancer-PRE association in transcription status transition of
during midbrain
development. Takashi Kondo
Haruhiko Koseki. Department of Developmental Genetics, RIKEN-RCAI, Yokohama,
Kanagawa, Japan.
Recent progress of genetics revealed that associations among remote
regulatory elements are necessary for proper
transcription regulation, although mechanisms of these processes remain unknown. We study
gene locus, a co-factor
genes, as a model system to study the remote DNA association processes. We identified a midbrain specific enhancer
element and a PRE (
responsive element) from 200Kb genomic sequence surrounding
locus in addition to a
promoter region. Combination of 3C (chromatin conformation capture), transgenic mouse, and FISH (and immuno-FISH) on
histological sections, we observed differences in associations of these DNA elements (the promoter, the enhance and the PRE)
corresponding to transcription statuses. Further analysis in developing midbrain revealed that step-wise associations of these
three DNA regions occurs during transition of transcription status.
The Histone Acetyltransferase MOF is a Key Regulator of the Embryonic Stem Cell Core Transcriptional
Network. Xiangzhi Li
Li Li
Yali Dou
. 1)
Institute of Cell Biology, School of Medicine, Shandong University, Jinan, China;
Rollins School of Public Health, Emory University, Atlanta, GA 30322; 3) Department of Pathology, University of Michigan,
Ann Arbor, MI 48109.
Self-renewal and pluripotency are hallmarks of embryonic stem cells (ESCs). Both ESCs features are subject to epigenetic
regulation. Here we show that histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and
pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining and differentiation
potential. They also have aberrant expression of core transcription factors Nanog, Oct4 and Sox2. Importantly, the phenotypes of
Mof null ESCs can be partially suppressed by Nanog overexpression, supporting that Mof functions as an upstream regulator of
Nanog in ESCs. Genome-wide ChIP sequencing and transcriptome analyses further demonstrate that Mof is an integral
component of ESC core transcription network and Mof primes genes for diverse developmental programs. Mof is also required