Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.
We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
Birney
Ewan
E
Stamatoyannopoulos
John A
JA
Dutta
Anindya
A
Guigó
Roderic
R
Gingeras
Thomas R
TR
Margulies
Elliott H
EH
Weng
Zhiping
Z
Snyder
Michael
M
Dermitzakis
Emmanouil T
ET
Thurman
Robert E
RE
Kuehn
Michael S
MS
Taylor
Christopher M
CM
Neph
Shane
S
Koch
Christoph M
CM
Asthana
Saurabh
S
Malhotra
Ankit
A
Adzhubei
Ivan
I
Greenbaum
Jason A
JA
Andrews
Robert M
RM
Flicek
Paul
P
Boyle
Patrick J
PJ
Cao
Hua
H
Carter
Nigel P
NP
Clelland
Gayle K
GK
Davis
Sean
S
Day
Nathan
N
Dhami
Pawandeep
P
Dillon
Shane C
SC
Dorschner
Michael O
MO
Fiegler
Heike
H
Giresi
Paul G
PG
Goldy
Jeff
J
Hawrylycz
Michael
M
Haydock
Andrew
A
Humbert
Richard
R
James
Keith D
KD
Johnson
Brett E
BE
Johnson
Ericka M
EM
Frum
Tristan T
TT
Rosenzweig
Elizabeth R
ER
Karnani
Neerja
N
Lee
Kirsten
K
Lefebvre
Gregory C
GC
Navas
Patrick A
PA
Neri
Fidencio
F
Parker
Stephen C J
SC
Sabo
Peter J
PJ
Sandstrom
Richard
R
Shafer
Anthony
A
Vetrie
David
D
Weaver
Molly
M
Wilcox
Sarah
S
Yu
Man
M
Collins
Francis S
FS
Dekker
Job
J
Lieb
Jason D
JD
Tullius
Thomas D
TD
Crawford
Gregory E
GE
Sunyaev
Shamil
S
Noble
William S
WS
Dunham
Ian
I
Denoeud
France
F
Reymond
Alexandre
A
Kapranov
Philipp
P
Rozowsky
Joel
J
Zheng
Deyou
D
Castelo
Robert
R
Frankish
Adam
A
Harrow
Jennifer
J
Ghosh
Srinka
S
Sandelin
Albin
A
Hofacker
Ivo L
IL
Baertsch
Robert
R
Keefe
Damian
D
Dike
Sujit
S
Cheng
Jill
J
Hirsch
Heather A
HA
Sekinger
Edward A
EA
Lagarde
Julien
J
Abril
Josep F
JF
Shahab
Atif
A
Flamm
Christoph
C
Fried
Claudia
C
Hackermüller
Jörg
J
Hertel
Jana
J
Lindemeyer
Manja
M
Missal
Kristin
K
Tanzer
Andrea
A
Washietl
Stefan
S
Korbel
Jan
J
Emanuelsson
Olof
O
Pedersen
Jakob S
JS
Holroyd
Nancy
N
Taylor
Ruth
R
Swarbreck
David
D
Matthews
Nicholas
N
Dickson
Mark C
MC
Thomas
Daryl J
DJ
Weirauch
Matthew T
MT
Gilbert
James
J
Drenkow
Jorg
J
Bell
Ian
I
Zhao
XiaoDong
X
Srinivasan
K G
KG
Sung
Wing-Kin
WK
Ooi
Hong Sain
HS
Chiu
Kuo Ping
KP
Foissac
Sylvain
S
Alioto
Tyler
T
Brent
Michael
M
Pachter
Lior
L
Tress
Michael L
ML
Valencia
Alfonso
A
Choo
Siew Woh
SW
Choo
Chiou Yu
CY
Ucla
Catherine
C
Manzano
Caroline
C
Wyss
Carine
C
Cheung
Evelyn
E
Clark
Taane G
TG
Brown
James B
JB
Ganesh
Madhavan
M
Patel
Sandeep
S
Tammana
Hari
H
Chrast
Jacqueline
J
Henrichsen
Charlotte N
CN
Kai
Chikatoshi
C
Kawai
Jun
J
Nagalakshmi
Ugrappa
U
Wu
Jiaqian
J
Lian
Zheng
Z
Lian
Jin
J
Newburger
Peter
P
Zhang
Xueqing
X
Bickel
Peter
P
Mattick
John S
JS
Carninci
Piero
P
Hayashizaki
Yoshihide
Y
Weissman
Sherman
S
Hubbard
Tim
T
Myers
Richard M
RM
Rogers
Jane
J
Stadler
Peter F
PF
Lowe
Todd M
TM
Wei
Chia-Lin
CL
Ruan
Yijun
Y
Struhl
Kevin
K
Gerstein
Mark
M
Antonarakis
Stylianos E
SE
Fu
Yutao
Y
Green
Eric D
ED
Karaöz
Ulaş
U
Siepel
Adam
A
Taylor
James
J
Liefer
Laura A
LA
Wetterstrand
Kris A
KA
Good
Peter J
PJ
Feingold
Elise A
EA
Guyer
Mark S
MS
Cooper
Gregory M
GM
Asimenos
George
G
Dewey
Colin N
CN
Hou
Minmei
M
Nikolaev
Sergey
S
Montoya-Burgos
Juan I
JI
Löytynoja
Ari
A
Whelan
Simon
S
Pardi
Fabio
F
Massingham
Tim
T
Huang
Haiyan
H
Zhang
Nancy R
NR
Holmes
Ian
I
Mullikin
James C
JC
Ureta-Vidal
Abel
A
Paten
Benedict
B
Seringhaus
Michael
M
Church
Deanna
D
Rosenbloom
Kate
K
Kent
W James
WJ
Stone
Eric A
EA
Batzoglou
Serafim
S
Goldman
Nick
N
Hardison
Ross C
RC
Haussler
David
D
Miller
Webb
W
Sidow
Arend
A
Trinklein
Nathan D
ND
Zhang
Zhengdong D
ZD
Barrera
Leah
L
Stuart
Rhona
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DC
Ameur
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A
Enroth
Stefan
S
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Mark C
MC
Kim
Jonghwan
J
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Akshay A
AA
Jiang
Nan
N
Liu
Jun
J
Yao
Fei
F
Vega
Vinsensius B
VB
Lee
Charlie W H
CW
Ng
Patrick
P
Shahab
Atif
A
Yang
Annie
A
Moqtaderi
Zarmik
Z
Zhu
Zhou
Z
Xu
Xiaoqin
X
Squazzo
Sharon
S
Oberley
Matthew J
MJ
Inman
David
D
Singer
Michael A
MA
Richmond
Todd A
TA
Munn
Kyle J
KJ
Rada-Iglesias
Alvaro
A
Wallerman
Ola
O
Komorowski
Jan
J
Fowler
Joanna C
JC
Couttet
Phillippe
P
Bruce
Alexander W
AW
Dovey
Oliver M
OM
Ellis
Peter D
PD
Langford
Cordelia F
CF
Nix
David A
DA
Euskirchen
Ghia
G
Hartman
Stephen
S
Urban
Alexander E
AE
Kraus
Peter
P
Van Calcar
Sara
S
Heintzman
Nate
N
Kim
Tae Hoon
TH
Wang
Kun
K
Qu
Chunxu
C
Hon
Gary
G
Luna
Rosa
R
Glass
Christopher K
CK
Rosenfeld
M Geoff
MG
Aldred
Shelley Force
SF
Cooper
Sara J
SJ
Halees
Anason
A
Lin
Jane M
JM
Shulha
Hennady P
HP
Zhang
Xiaoling
X
Xu
Mousheng
M
Haidar
Jaafar N S
JN
Yu
Yong
Y
Ruan
Yijun
Y
Iyer
Vishwanath R
VR
Green
Roland D
RD
Wadelius
Claes
C
Farnham
Peggy J
PJ
Ren
Bing
B
Harte
Rachel A
RA
Hinrichs
Angie S
AS
Trumbower
Heather
H
Clawson
Hiram
H
Hillman-Jackson
Jennifer
J
Zweig
Ann S
AS
Smith
Kayla
K
Thakkapallayil
Archana
A
Barber
Galt
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Karolchik
Donna
D
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Lluis
L
Bird
Christine P
CP
de Bakker
Paul I W
PI
Kern
Andrew D
AD
Lopez-Bigas
Nuria
N
Martin
Joel D
JD
Stranger
Barbara E
BE
Woodroffe
Abigail
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Davydov
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E
Dimas
Antigone
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Eyras
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E
Hallgrímsdóttir
Ingileif B
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Michael C
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Abecasis
Gonçalo R
GR
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Gerard G
GG
Guan
Xiaobin
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Nancy F
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Valerie V B
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DM
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Erica
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David A
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Kim C
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George M
GM
Gibbs
Richard A
RA
Graves
Tina
T
Fulton
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R
Mardis
Elaine R
ER
Wilson
Richard K
RK
Clamp
Michele
M
Cuff
James
J
Gnerre
Sante
S
Jaffe
David B
DB
Chang
Jean L
JL
Lindblad-Toh
Kerstin
K
Lander
Eric S
ES
Koriabine
Maxim
M
Nefedov
Mikhail
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Osoegawa
Kazutoyo
K
Yoshinaga
Yuko
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Zhu
Baoli
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de Jong
Pieter J
PJ
D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence / Q000235:genetics; D004261:DNA Replication; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006579:Heterozygote; D006657:Histones / Q000378:metabolism; D006801:Humans; D010865:Pilot Projects; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics*
D002843:Chromatin; D006657:Histones; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014157:Transcription Factors