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saturn

孤陋寡闻一下了，不知道楼上的说的那个( Y( p4 `+ R' M1 l  T
表观遗传学主要研究转录前基因在染色质水平的结构修饰对基因功能的影响/ O! ?% [, t0 k' o7 j
这个定义是从哪看到的呀，可以给个出处吗，这可是第一次看到这个说法？个人感觉epigegenetic might include three respects: DNA methylation, histone modification and non-coding RNA, therefore, miRNA also should be included in non-coding RNA. And now there are also several papers published in this year present miRNA also could affect DNA methylation in transcriptional level not only in post transcriptional level.

saturn

first i am not a expert, just for interest.% j" Q/ O% ?0 L+ {9 S) z. |/ V
second your question confused me, for the sentence of epigenetic definition you wondered i could not show you a link at the moment, however, if you are really interested in the epigenetic field, you might see the similar sentence in plenty of papers, even in BIG BULLS' reviews. in my opinion, the reference you mentioned in your post, i didn't agree with that at all. i don't think it is a good book in epigenetic.
/ H# E' L$ B! ~+ |& d- o! ]finally, i really could not understand the last sentence. could you say it more details?

saturn

回复  saturn
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3 ?3 j9 F! H# `) E8 B- w3 W  k    看来你对我言简意赅的表述非常不解，“因为non-coding RNA所以miRNA？”这句话的意思 ...3 R( l, Q4 D* P9 U
kittybruce 发表于 2010-5-1 15:09

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我知道问题出在哪了，是我说的有歧义，therefore, miRNA also should be included in non-coding RNA 我加了一个therefore, 换成however 应该没有歧义了吧？我先要承认自己的错误。
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我的意思是说表观包括3方面，而noncoding RNA是包括miRNA的，或者是miRNA也包括在non-coding RNA 里面的，不过如果朋友认为miRNA不属于non-coding RNA,那这个问题就没有必要进行下去了。. R0 l4 v+ m8 \- _& y& E

( J" F  \& Q$ C2 P3 j7 L3 I还有一个问题就是如果要是作为学习资料的话，个人认为应该尽量看一些权威的书，有些书籍杂志不看也罢。

saturn

呵呵，楼上的兄弟不要讨论这个问题了，每个人的看法是不同的，估计Hannon or Bartel告诉他这个问题，他可能都不这么认为，所以我才没有继续和他说下去。
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0 r4 G9 |) o/ A- ?  `5 R% |就让我们结束这个话题吧

saturn

我们先不说什么权威不权威吧，先科普一下，
0 @5 k$ G; O  p* L2 S! kepigenetics is the study of inherited  changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA  sequence,这个定义是wiki里面的，应该是大家普遍比较承认的吧。3 f$ u+ h6 ^8 L3 r
先不谈phenotype只说gene expression。+ C3 b& J* l5 u; y
previous study only show that siRNA could play a role both in TGS and PTGS, but recently several papers also show that miRNA could also affect gene expression in transcriptional level rather than only in Post transcriptional level.
" m( c( u; W& _这里有个问题就是RNAi你认不认为是属于epigenetic范畴的，如果你不认为它属于epigenetic field，那这个问题就不用讨论了，如果你也认为它属于，那你认为miRNA是不是在RNAi中期重要作用的呢？7 ^0 q( B! C* S4 l9 {5 D; S
这不是一个go with flow的问题，你能拿出证据说明问题，那非常好的，真理往往掌握在少数人手中，但前提是你要有充分的证据说明你的观点，. e2 b2 I) B, t+ o# A
按照表观遗传学的定义，无论是siRNA 还是miRNA都应该符合吧，你能指出他不符合的依据吗，

saturn

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for your first question, i think the usual sentence might be epigenetic regulation of gene expression ……， i don't think you have seen the epigenetic mechanism of DNA methylation, histone modification or non-coding RNA in the regulation of ……， such kinds of sentences.
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" ?5 e/ E) o0 r1 x; X) ]. vfor the second question,  one paper is published by Yijun Qi in NIBS
5 y1 s# q3 w; c1 u, o9 l" QDNA Methylation Mediated by a MicroRNA Pathway.
1 P; S  }' k$ z* L+ b7 R' `$ c3 Q) xWu L, Zhou H, Zhang Q, Zhang J, Ni F, Liu C, Qi Y.
$ ^* c+ Z% f, H* wMol Cell. 2010 Apr 7. [Epub ahead of print]0 n/ U6 n, @* M7 N, i4 b
another paper is published in cell
' u: l5 A' o; _) b; C- ^Transcriptional control of gene expression by microRNAs.
( i8 Q3 z1 d' X" J; GKhraiwesh B, Arif MA, Seumel GI, Ossowski S, Weigel D, Reski R, Frank W.
2 l' i: x; W) b3 ICell. 2010 Jan 8;140(1):111-22.
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although you might argue that these two papers are only in plants, i think miRNA should play a conserved role in evolution. by the way, there are also some other similar papers, you could find them in pubmed yourself.% W! _6 t) M5 E3 T

8 R5 P9 o2 A: O# X1 I4 X! |personally i think there will be nobody agree with the narrow definition you listed before, RNAi should be involved in epigenetic, and it plays a role in PTGS.) k9 _; r9 \, C. K; i

9 B8 N) `. B+ d) W( Q' A% S, O# Whave fun in epigenetic field!

saturn

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here are several publications elucidate miRNA is an epigenetic regulator* y, D$ ^8 N$ {) P& N7 p6 s
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Review
% G2 G0 N! q2 xEpigenetic mechanisms in glioblastoma multiforme
  |; P! v) Q% ^) P1 D7 WRaman P. Nagarajana and Joseph F. CostelloCorresponding Author Contact Information, a, E-mail The Corresponding Author
/ ?! D+ U: H( ~+ d9 LaBrain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA
% b; _2 N( P0 `5 O& x6 z; oAvailable online 20 February 2009.
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2.7. Aberrant expression of microRNAs in GBM
0 [8 J% x3 U2 j6 _4 g3 kMicroRNAs (miRNAs), non-coding RNAs which are potential epigenetic regulatory effectors, are important in normal mammalian development and dysregulation of their expression has been observed in multiple human cancers. MiRNAs are 19–25 nt in length and are cleaved from 60–110 nt hairpin precursors (pre-miRNAs) derived from larger primary transcripts (pri-miRNAs). MiRNAs can regulate gene expression through interactions with mRNAs in regions of sequence complementary, blocking translation of mRNAs [103].
4 t6 k7 q- r/ K) y4 I! k. q4 ~In GBM, multiple miRNAs are aberrantly expressed or repressed in both primary tumors and cell lines [104]. Primary GBMs and cell lines overexpress miR-221, whereas a set of brain-enriched miRNAs (miR-128, miR-181a, miR-181b, and miR-181c) shows decreased expression [105]. Reduced miR-128 expression in GBM and consequent reduced cell proliferation in vitro and in xenografts [106] were shown in a separate study. Furthermore, miR-128 regulates the expression of the polycomb complex protein Bmi-1 through binding at the BMI-1 3′-UTR, resulting in decreased Bmi-1 and H3K27me3 levels. In GBM-derived neurosphere cells, miR-128 overexpression blocked stem cell self-renewal, indicating that miR-128 can regulate the stem cell-like capabilities of a subset of GBM cells.  g, s9 _7 y; L5 G5 S) j
Additional microRNAs are aberrantly expressed in GBM. MiR-124 and miR-137 are underexpressed in primary GBM and anaplastic astrocytoma [107]. MiR-137 expression was increased in GBM cell lines U87 and U251 following treatment with 5-aza-2′-deoxycytidine, suggesting regulation of these microRNAs by DNA methylation. Functionally, miR-124 and miR-137 inhibit proliferation in GBM and can induce differentiation of normal neural and brain tumor stem cells. Additional studies have demonstrated that miR-124 is underexpressed in primary oligodendrogliomas, astroblastomas, and GBM cell lines [108], [109] and [110] indicating a potentially central role for this non-coding RNA in brain tumors. Overall, microRNAs appear to play multiple roles in cancer biology; for example in GBM miR-21 has both anti-apoptotic and pro-invasion functions
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The microRNA network and tumor metastasis" o* ]4 ~7 H: B, E$ E+ ?( _" ?
H Zhang, Y Li and M Lai5 N; \% P7 x+ A6 I0 v4 _4 y2 e
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China4 D! z( |& [' f$ ^$ m

2 j/ J, M1 {9 g; LThe reciprocal regulation between miRNA and epigenetic modification in tumor metastasis6 p  K; H* m% j4 x9 p* c8 \
Epigenetic modifications include DNA methylation and covalent modification of histones. These alterations are reversible, but very stable, and have a significant impact on the regulation of gene expression, the contribution of which to cancer goes beyond the early stages of tumor transformation to affect metastasis. However, miRNAs have an important role in epigenetic modification, and are also regulated by epigenetic mechanisms in tumor metastasis.
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) K6 \( T$ q# m' s3 wNature Reviews Rheumatology 5, 266-272 (May 2009) | doi:10.1038/nrrheum.2009.55
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Epigenetic control in rheumatoid arthritis synovial fibroblasts& l) Q$ i( T6 ^7 D; k
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Emmanuel Karouzakis, Renate E. Gay, Steffen Gay & Michel Neidhart0 _% n2 [' E" y* y# ^
Abstract
/ ^. {  k0 }  A, bRheumatoid arthritis synovial fibroblasts (RASFs) are the effector cells of cartilage and bone destruction. These cells show an 'intrinsically' activated and aggressive phenotype that results in the increased production of matrix-degrading enzymes and adhesion molecules, and is conserved over long-term passage in vitro. The three main mechanisms of epigenetic control—DNA methylation, histone modifications and microRNA activity—interact in the development of the RASF phenotype. The extent of global DNA methylation is reduced in synoviocytes in situ and RASFs in vitro. In addition, histone hyperacetylation occurs and specific microRNAs are expressed in RASFs. Normal synovial fibroblasts cultured in a hypomethylating milieu acquire an activated phenotype similar to that of RASFs. These findings suggest that epigenetic control, in particular the control of DNA methylation, is deficient in RASFs. Genome-wide analyses of the epigenome will enable the detection of additional genes involved in the pathogenesis of rheumatoid arthritis, the identification of epigenetic biomarkers, and potentially the development of a therapeutic regimen that targets activated RASFs.# @/ }0 W5 i$ R3 M) `# x
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Leukaemogenesis:more than mutant genes
  Y* L5 d: B+ ?! BJianjun Chen*§, Olatoyosi Odenike*§ and Janet D. Rowley*‡& q4 |) p* N: y9 \$ L2 K" y$ ^
Abstract | Acute leukaemias are characterized by recurring chromosomal aberrations andgene mutations that are crucial to disease pathogenesis. It is now evident that epigenetic modifications, including DNA methylation and histone modifications, substantially contribute to the phenotype of leukaemia cells. An additional layer of epigenetic complexity is the pathogenetic role of microRNAs in leukaemias, and their key role in the transcriptional regulation of tumour suppressor genes and oncogenes. The genetic heterogeneity of acute leukaemias poses therapeutic challenges, but pharmacological agents that target components of the epigenetic machinery are promising as a component of the therapeutic arsenal for this group of diseases.
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; p. v# @$ x+ `% o3 j9 u% fhope for your comments, by the way could you list some evidences show that miRNA is not an epigenetic effector?(from the expert you mentioned)

saturn

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5 B2 \. e, d$ k1 i+ F. Fto be honest,  i pay less attention to the definition of epigenetic(strict definition), however, personally i think the most important thing in the definition is to  regulate gene expression without changes in DNA sequence, i also think this is accepted by all the researchers in this field. 0 w  X2 P* X, q5 g2 l/ Z

, j  }3 j: T) D6 |and i also have an another requirement, could you list some exact the same sentence in you last post, such as epigenetic mechanism of DNA methylation or histone modification in the regulation of…… in any papers is OK.# P, ?$ @0 @; a: Y( z
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nothing in the world is absolutely!

saturn

here is also another interesting paper related paramutation, also controlled by miRNA& T/ a: J, E1 m6 m% A- h, W

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6 b/ x. }; m7 a( ^5 P( G, \( Kby the way, if you are really interested, you could search miRNA epigenetic in pubmed, then you could find plenty of papers.% b# Z9 z* q( W  \0 v8 B

/ n( K. G% E, ?it is a little funny to discuss this topic with a person who are not in epigenetic field, if you have read some important papers in this field, i suppose you should not ask such a silly question.

saturn

hehe, first i want to say i am not angry with you, i don't know why you said i was irritated,
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, C# O& i7 v( W9 U6 t6 i, \second i was wondering why the evidences i showed are not convincing, i think they are all published in good journals, at least better or higher influence than the modern immunology you mentioned before.
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8 T: t- U  @( s, I; p: E. \9 Z6 N9 b: y9 @third, don't you think it is a silly question. if you have more knowledge in epigenetic field, you could never ask such a kind of question.
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1 |* p, S, m& ^! Lfinally, i think i am the first one want to end this discussion with you.; E) N8 ^$ f* Q! n" b* _# k: N8 @8 C- e

4 h; ^1 y9 H& ?" Mhowever, now you could not show any evidence that support your layman's point, you just said i was too busy to discuss with you.
/ w  O6 D9 R" v5 Y3 u3 Uok let's stop ! 2 `9 x6 [; r6 v! v
everyone is too busy with their experiments, not only you.
2 e9 Q0 I9 `; Z  h$ Kby the way, some time when you have a chance to discuss with the others i think you have to treasure it,  you might learn something from the discussion,  B1 M# |6 K2 d9 _- ]) X! F
it is meaningful!
7 b2 {' @5 Z7 F! M+ Q- bthat is why so many conferences exist!
, j/ I3 t7 G; h: K+ P i hope next time if you want to discuss something with the others please make sure that you know that field well. and do please not say anything you have no evidence to support your point!