UCLA Prof. Sun YE's recent Science paper

lixiaodong

Science. 2010 Jul 23;329(5990):444-8.
7 ^8 W# p1 M& w, Q% D3 q/ x8 l5 YDnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes.8 X8 |& T, U& \4 b* L! v$ B
Wu H, Coskun V, Tao J, Xie W, Ge W, Yoshikawa K, Li E, Zhang Y, Sun YE.( k) h4 g6 p% R" N2 ]9 X
Department of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA. haowu7@gmail.com
; N( z9 |) O. T: X' U- \( l% c$ L1 [+ v$ x- ]- R$ K
Abstract
+ G2 a1 t( \' ^0 ~8 x( KDNA methylation at proximal promoters facilitates lineage restriction by silencing cell type-specific genes. However, euchromatic DNA methylation frequently occurs in regions outside promoters. The functions of such nonproximal promoter DNA methylation are unclear. Here we show that the de novo DNA methyltransferase Dnmt3a is expressed in postnatal neural stem cells (NSCs) and is required for neurogenesis. Genome-wide analysis of postnatal NSCs indicates that Dnmt3a occupies and methylates intergenic regions and gene bodies flanking proximal promoters of a large cohort of transcriptionally permissive genes, many of which encode regulators of neurogenesis. Surprisingly, Dnmt3a-dependent nonproximal promoter methylation promotes expression of these neurogenic genes by functionally antagonizing Polycomb repression. Thus, nonpromoter DNA methylation by Dnmt3a may be used for maintaining active chromatin states of genes critical for development.1 c4 |' q! N  |2 ]2 K( e$ \4 t+ H

# x5 e+ C9 z# h. DThe second paper is her group's earlier work.- b  X. q( R7 m$ u; x5 x: D* A% g
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13821-6. Epub 2007 Aug 10.
' N7 m( ?7 u# E. G9 W, v* i) \Integrative genomic and functional analyses reveal neuronal subtype differentiation bias in human embryonic stem cell lines.
: ?1 }' i4 j9 SWu H, Xu J, Pang ZP, Ge W, Kim KJ, Blanchi B, Chen C, Südhof TC, Sun YE.
: l5 i$ W& n- ~3 T4 @, ^: PMental Retardation Research Center, David Geffen School of Medicine at University of California, Los Angeles, Neuroscience Research Building Room 351, 635 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
; L% Y" u6 T, ^5 W# [* E( R1 {Abstract
1 Z" u  m; a& U6 CThe self-renewal and differentiation potential of human embryonic stem cells (hESCs) suggests that hESCs could be used for regenerative medicine, especially for restoring neuronal functions in brain diseases. However, the functional properties of neurons derived from hESC are largely unknown. Moreover, because hESCs were derived under diverse conditions, the possibility arises that neurons derived from different hESC lines exhibit distinct properties, but this possibility remains unexplored. To address these issues, we developed a protocol that allows stepwise generation from hESCs of cultures composed of approximately 70-80% human neurons that exhibit spontaneous synaptic network activity. Comparison of neurons derived from the well characterized HSF1 and HSF6 hESC lines revealed that HSF1- but not HSF6-derived neurons exhibit forebrain properties. Accordingly, HSF1-derived neurons initially form primarily GABAergic synaptic networks, whereas HSF6-derived neurons initially form glutamatergic networks. microRNA profiling revealed significant expression differences between the two hESC lines, suggesting that microRNAs may influence their distinct differentiation properties. These observations indicate that although both HSF1 and HSF6 hESCs differentiate into functional neurons, the two hESC lines exhibit distinct differentiation potentials, suggesting that they are preprogrammed. Information on hESC line-specific differentiation biases is crucial for neural stem cell therapy and establishment of novel disease models using hESCs.

tspaulzhao

Thanks a lot.

tspaulzhao

Thanks a lot.