人X染色体长臂_Xq_和短臂_Xp_基因组学比较分析_英文__cropped

遗 传 学 报

Acta Genetica Sinica , J anuary 2005 , 32

(

1

)

: 1

～

10

ISSN 0379 - 4172

Ge n o m e S e q u e n c e C o mp a r a ti ve A n al ys i s of L o n g Ar m

a n d S h o rt Ar m of Hu m a n

X C h r o m o s o m e

①

L

Β

Zhan

2

J un , SONG Shu

2

Xia , ZHAI Yu , HOU J ie ,

HAN Li

2

Zhi , WANG Xiu

2

Fang

(

Department of L aboratory Animal , Hebei Medical University , S hijiazhuang

050017

, China

)

A b s t r a c t : 30 % of the ge ne s te ste d o n Xp e scap e d inactivatio n ,where a s le s s tha n 3 % of the ge ne s o n Xq e scap e d in

2

activatio n . To inve stigate the molecular mecha ni sm involve d in the prop a gatio n a nd mainte na nce of X chro mo so me inac

2

tivatio n a nd e scap e ,the lo ng arm a nd short arm of the X chro mo so me were co mp are d for RNA binding de n sity. Nu

2

cleotide se que nce s o n the X chro mo so me were divide d into 50 kb p er se gme nt that wa s recorde d a s a set of fre que ncy

value s of 7

2

nucleotide

(

7 nt

)

string s u sing all po s sible 7 nt string s

(

4

7

= 16 384

)

. 120 ge ne s highly expre s se d in the to n sil

germinal ce nter B cell s were selecte d for calculating the 7 nt string fre que ncy value s of all intro n s

(

intro n 7nt

)

. Intro n 7nt

wa s co n sidere d RNAs

(

RNA pop ulatio n

)

that simulate d the total of small RNA fra gme nt s in cell s . Knowing the 7 nt fre

2

que ncy value s of DNA se gme nt s a nd the intro n 7nt ,we ca n calculate the binding de n sity of DNA se gme nt s to the intro n

7nt that wa s terme d a s RNA binding de n sity. The RNA binding de n sity wa s determine d by the a mo unt of co mple me nt

se que nce s. The more a mo unt of co mple me nt se que nce s , the more de n sity of RNA binding. The RNA binding de n sity

simulate d the total of small RNA fra gme nt s bo und to the DNA se gme nt . Several princip al characteri stic s were o b serve d

for the fir st time :

(

1

)

The me a n value of RNA binding de n sity of DNA se gme nt s o n Xp wa s significa ntly higher tha n that

o n Xq

(

P < 0

1

001

)

;

(

2

)

The number s of DNA se gme nt s highly binding RNAs were more o n Xp tha n o n Xq

(

P <

0

1

001

)

;

(

3

)

The clu ster s of RNA highly binding DNA se gme nt s were a s so ciate d with re gio n s in which ge ne s e scap e in

2

activatio n. It ha s be e n sugge ste d that RNAs activate ge ne s a nd the interactio n of RNA

2

DNA in cell s are exte n sive ,for

exa mple , RNAs incre a se DNa se

Ⅰ

se n sitivity of DNA , there i s ple nty of no nprotein

2

co ding RNAs in cell s , the binding

sp ecificity of DNA

2

RNA i s f ar higher tha n that of DNA

2

protein a nd the affinity of DNA with RNA i s incre a se d , a s co m

2

p are d with DNA. The no nra ndo m prop ertie s of di stributio n of RNA highly binding se gme nt s betwe e n Xp a nd Xq , co m

2

bine d with the finding of RNA activating ge ne s ,pro vide a stro ng evide nce that RNA highly binding se gme nt s may serve

a s DNA signal s to prop a gate activatio n alo ng a chro mo so me a nd vice ver sa ,the DNA se gme nt s that le s s bind RNAs

may sile nce the ge ne s .

Ke y w o r d s : Xp ; Xq ; inactivatio n e scap e ; intro n RNA ; nucleotide string

收稿日期

:2004 - 03 - 08 ;

修回日期

:2004 - 09 - 02

作者简介

:

吕占军

(

1952 -

)

男

,

博士生导师

,

河北省免疫学会副理事长

,

研究方向

:

衰老 、分化和肿瘤发生理论及抗衰老 、抗肿瘤对策研究

① 通讯作者 。

E

2

mail:***************.cn;Tel :0311

2

6055020 ,0311

2

6266844

人

X

染色体长臂

(

Xq

)

和短臂

(

Xp

)

基因组学比较分析

吕占军

①

,

宋淑霞

,

翟 羽

,

侯 杰

,

韩丽枝

,

王秀芳

(

河北医科大学实验动物学部

,

石家庄

050017

)

摘 要

: X

染色体发生

X

染色体失活

,

但是

Xp

基因有

30 %

表现为逃逸

,

而

Xq

仅不到

3 %

。为了研究

X

染色体基因

失活和表达逃逸发生和维持的分子机制

,

比较了

Xq

和

Xp DNA

序列的

RNA

模拟结合强度 。

X

染色体的核苷酸序列

被分为

50 kb

一段

,

对每一段

DNA

做

7

碱基

(

7 nt

)

字符串组合分析

(

共有

4

7

= 16 384

种组合

)

,

记录每段

50 kb DNA

中每种

7 nt

字符串的频率 。选择生发中心

B

细胞中的

120

个高表达基因

,

计算这些基因的内含子

7 nt

字符串的出

现频率

,

称为

intron 7nt ,

以此作为

RNAs

(

RNA

群

,

模拟细胞中

RNA

在小片段的总和

)

。已知一段

DNA

序列的

7 nt

频

率值和

intron 7nt ,

即可以计算该

DNA

段与

intron 7nt

的结合强度 。每段

50 kb DNA

与

intron 7nt

的结合强度取决于该

DNA

段与

intron 7nt

互补核苷酸的频率

,

互补的核苷酸序列越多

,

结合强度就越大 。

DNA

段与

intron 7nt

的模拟结合

强度称为

RNA

结合强度

,

试图模拟该段

DNA

可以结合的

RNA

小片段的总量 。之所以采用

7 nt

字符串组合分析是

考虑到连续

7

个核苷酸互补则可以形成相对稳定的结合 。研究发现

: 1

)

Xp

各

DNA

段的

RNA

结合强度均值显著大

于

Xq

(

P < 0

1

001

)

;2

)

Xp

上高结合

RNA

的

DNA

段数目显著高于

Xq

(

P < 0

1

001

)

;3

)

RNA

高结合

DNA

段形成的簇与

X

染色体基因表达逃逸区关联 。有证据表明

,RNA

可以通过改变染色质构象活化基因并且该作用具有普遍意义

:

如

RNA

增加染色质对

DNase

Ⅰ消化的敏感性

,

互补

RNA

2

DNA

的亲和性高于互补

DNA

2

DNA ,

细胞中有丰富的非编码

RNA

和非编码

DNA

等 。研究中的发现结合

RNA

活化基因的观点

,

提示

Xp

逃逸失活基因的数目多于

Xq

可能与前

者的

RNA

结合强度大于后者有关 。

关键词

: X

染色体长臂

; X

染色体短臂

;

失活逃逸

;

内含子

RNA ;

核苷酸字符串

中图分类号

: Q347

文献标识码

: A

文章编号

: 0379

2

4172

(

2005

)

01

2

0001

2

10

X chromosome inactivation

(

XCI

)

is the process

whereby one of the two X chromosomes in normal diploid

female cells is inactivated to compensate for the dosage

difference of X

2

linked genes between males and females.

One of the most intriguing aspects of X inactivation in hu

2

mans is that certain genes have been found that escape in

2

activation and are expressed from both X chromosomes

1

.

The genes that escape inactivation

(

expressed from both

the active and inactive X chromosomes

)

are nonrandomly

distributed ,with the majority of such transcripts mapping

to the short arm on X chromosome and not to the long

arm

2 ,3

Although the basis for the expression of these genes

from the inactive X chromosome is unclear at present ,

their study is likely to be informative for understanding the

chromosomal mechanisms involved in X inactivation , im

2

plying the existence of local and/ or chromosomal signals

that are subjected to inactivation.

that distinguish genes that escape inactivation from those

To investigate the molecular mechanism involved in

the propagation and maintenance of X chromosome inacti

2

vation and escape ,the long arm and short arm of X chro

2

computer simulation of binding density of DNA segments

and RNAs at 7 nt string level .

mosome were compared for RNA binding density being a

. 30 % of the genes tested on Xp escaped inactiva

2

tion ,whereas less than 3 % of the genes on Xq escaped

inactivation

4

.