Dae-Soo Kim1, Jae-Won Huh2 ,Hong-Seok Ha1, Kung Ahn1, Yun-Ji Kim1, Ja-Rang Lee1, and Heui-Soo Kim1, 2

1PBBRC, Interdisciplinary Research Program of Bioinformatics, College of Natural Sciences, Pusan National University, Busan 2Division of Biological Sciences, College of Natural Sciences,Pusan National University, Busan

In Silico Analysis of Transposable Elements Expression in Human Cancer

Molecular Biology & Genome Information Lab.

ABSTRACTTransposable elements are the most abundant interspersed sequences in human genome. It has been estimated that approximately 45% of the human genome comprises of transposable elements. Most of transposable elements are transcriptionally silent in human normal tissues, however, some of transposable elements have been found to be expressed in placenta tissues and cancer cell lines. Recent studies have shown that transposable elements could affect coding sequences, splicing patterns, and transcriptional regulation of human genes. In the present study, we investigated the transposable elements in relation to human cancer. Our analysis pipeline adopted for screening methods of the cancer specific expression from human expressed sequences. We developed a database for understanding the mechanism of cancer development in relation to transposable elements. Totally, 999 genes were identified to be integrated in their mRNA sequences by transposable element. We believe that our work might help many scientists who interested in cancer research to gain the insight of transposable element for understanding the human cancer.

RESEARCH AIMSMost of TEs are transcriptionally silent in human normal tissues, however, some of TEs have been found to be expressed in placenta tissues and cancer cell lines. The L1 antisense promoter-driven transcription has been detected in human tumor cells or normal ones, while HERV LTR elements have shown the bidirectional promoter activity (Medstrand et al., 2001; Nigumann et al., 2002; Dunn et al., 2003; Sin et al., 2006). Those elements could provide biological role of organismal complexity by transcriptional diversity (Landry et al., 2003). Here, we developed a database for understanding the mechanism of cancer development in relation to TEs in human EST sequences.

RESULTS & DISCUSSION

http://www.primate.or.kr

13.6%

3.8%1.6% 0.7% 0.2% 0.1% 0.1%

79.8%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

1 2 3 4 5 6 11 17

Transposable element fuion EST counts

Gen

es

%

11%

82%

6%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

5′UTR CDS 3′UTR

Location of transposable elements fusion EST

Percen

t o

f ex

on

s %

http://www.primate.or.kr/

ATGCA

AT

MATERIALS & METHODS

Transposable elements fusion region within genes SINE Family LINE Family LTR Family DNA Family Others

CDS 619 280 85 76 1

5′UTR 76 30 33 5 0

3′UTR 44 20 14 5 0

Transposable elements

Table Distribution of transposable element family in region of transposable element exonization

5UTR CDS 3UTR

Alu 0 20 0

AluJ 20 131 12

AluS 13 190 15

AluY 3 37 5

MIR 33 198 7

FAM 0 2 0

FRAM 0 16 2

FLAM 7 25 3

HAL 0 11 0

L1HS 0 1 0

L1P 1 12 5

L1M 6 125 6

L2 22 111 7

L3 1 20 2

MaLR 16 40 6

ERV1 13 23 3

ERVL 4 16 5

ERVK 0 6 0

Charlie 0 9 0

HSMAR2 0 2 0

Kanga1 0 0 1

MARNA 0 3 0

MER 5 50 3

Tigger 0 11 1

Zaphod2 0 1 0

Others Charlie 0 1 0

Transposable elements fusion in gene region

DNA Family

LTR Family

LINE Family

SINE Family

Family Subfamily

Table Distribution of transposable elements into coding and untranslated region of gene

Table. EST based expression profiles of transposable elements in human cancer

Type of

potential splicing site SINE Family LINE Family LTR Family DNA FamilyAccept&Donor 83 68 50 12Accept Site 271 110 33 28Donor Site 216 80 43 18

Transposable elements

Table Potential splice site are utilized by transposable elements fusion exons

SUMMARY Through this update, we will be able to profile the patterns of transposable expression in various diseases and to understand the transposable element that have an effect on the expression of human functional genes. We believe that our work will help us gain insight into implication of TEs expression in human evolution and diseases.

Table. Distribution of transposable elements within cancer specific expression transcripts

Family SubfamilyAlu 20 1.44AluJ 171 12.35AluS 244 17.62MIR 250 18.05FAM 2 0.14

FRAM 18 1.30FLAM 37 2.67HAL 13 0.94L1HS 1 0.07L1P 18 1.30L1M 153 11.05L2 151 10.90L3 25 1.81

MaLR 67 4.84ERV1 40 2.89ERVL 27 1.95ERVK 6 0.43Charlie 9 0.65

HSMAR2 2 0.14Kanga1 1 0.07

MARNA 3 0.22MER 61 4.40Tigger 14 1.01

Zaphod2 1 0.07Others Charlie 1 0.07

SINE

LINE

LTR

DNA

Transposable elementsOccurrences Percent (%)

Database Construction

Long In

tersp

erse

d N

ucle

ar E

lem

ents (LIN

E) &

Short In

tersp

erse

d N

ucle

ar E

lem

ents (S

INE)

Hum

an E

ndogenous R

etro

viru

s (HER

V) &

Long T

erm

inal R

epeats (LT

R)

MATERIALS & METHODS

SUMMARIES AND FUTURE DIRECTIONSThrough this update, we will be able to profile the patterns of transposable expression in various diseases and to understand the transposable element that have an effect on the expression of human functional genes. We believe that our work will help us gain insight into implication of TEs expression in human evolution and diseases.

REFERENCESKim TH, Jeon YJ, Kim WY, Kim HS: HESAS: HERVs expression and structure analysis system. Bioinformatics 2005, 15:1699-1970.

Kim DS, Kim TH, Huh JW, Kim IC, Kim SW, Park HS, Kim HS : LINE FUSION GENES: a databaseof LINE expression in human genes. BMC Genomic 2006, 7:139

Figure Transposable elements fusion EST counts

Transposable elements fusion region within genes SINE Family LINE Family LTR Family DNA Family Others

CDS 619 280 85 76 15′UTR 76 30 33 5 03′UTR 44 20 14 5 0

Transposable elements

Table Distribution of transposable element family in region of transposable element exonization

5UTR CDS 3UTR

Alu 0 20 0

AluJ 20 131 12

AluS 13 190 15

AluY 3 37 5

MIR 33 198 7

FAM 0 2 0

FRAM 0 16 2

FLAM 7 25 3

HAL 0 11 0

L1HS 0 1 0

L1P 1 12 5

L1M 6 125 6

L2 22 111 7

L3 1 20 2

MaLR 16 40 6

ERV1 13 23 3

ERVL 4 16 5

ERVK 0 6 0

Charlie 0 9 0

HSMAR2 0 2 0

Kanga1 0 0 1

MARNA 0 3 0

MER 5 50 3

Tigger 0 11 1

Zaphod2 0 1 0

Others Charlie 0 1 0

Transposable elements fusion in gene region

DNA Family

LTR Family

LINE Family

SINE Family

Family Subfamily

Table Distribution of transposable elements into coding and untranslated region of gene

Table 3 EST based expression profiles of transposable elements in human cancer

Type of

potential splicing site SINE Family LINE Family LTR Family DNA FamilyAccept&Donor 83 68 50 12Accept Site 271 110 33 28Donor Site 216 80 43 18

Transposable elements

Table Potential splice site are utilized by transposable elements fusion exons

Database Construction