PMID- 24363063
OWN - NLM
STAT- MEDLINE
DCOM- 20141203
LR  - 20220129
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 23
IP  - 10
DP  - 2014 May 15
TI  - Disruption of SATB2 or its long-range cis-regulation by SOX9 causes a syndromic 
      form of Pierre Robin sequence.
PG  - 2569-79
LID - 10.1093/hmg/ddt647 [doi]
AB  - Heterozygous loss-of-function (LOF) mutations in the gene encoding the 
      DNA-binding protein, SATB2, result in micrognathia and cleft palate in both 
      humans and mice. In three unrelated individuals, we show that translocation 
      breakpoints (BPs) up to 896 kb 3' of SATB2 polyadenylation site cause a phenotype 
      which is indistinguishable from that caused by SATB2 LOF mutations. This syndrome 
      comprises long nose, small mouth, micrognathia, cleft palate, arachnodactyly and 
      intellectual disability. These BPs map to a gene desert between PLCL1 and SATB2. 
      We identified three putative cis-regulatory elements (CRE1-3) using a comparative 
      genomic approach each of which would be placed in trans relative to SATB2 by all 
      three BPs. CRE1-3 each bind p300 and mono-methylated H3K4 consistent with 
      enhancer function. In silico analysis suggested that CRE1-3 contain one or more 
      conserved SOX9-binding sites, and this binding was confirmed using chromatin 
      immunoprecipitation on cells derived from mouse embryonic pharyngeal arch. 
      Interphase bacterial artificial chromosome fluorescence in situ hybridization 
      measurements in embryonic craniofacial tissues showed that the orthologous region 
      in mice exhibits Satb2 expression-dependent chromatin decondensation consistent 
      with Satb2 being a target gene of CRE1-3. To assess their in vivo function, we 
      made multiple stable reporter transgenic lines for each enhancer in zebrafish. 
      CRE2 was shown to drive SATB2-like expression in the embryonic craniofacial 
      region. This expression could be eliminated by mutating the SOX9-binding site of 
      CRE2. These observations suggest that SATB2 and SOX9 may be acting together via 
      complex cis-regulation to coordinate the growth of the developing jaw.
FAU - Rainger, Jacqueline K
AU  - Rainger JK
AD  - MRC Human Genetics Unit, MRC Institute of Genetic and Molecular Medicine, 
      University of Edinburgh, Edinburgh EH4 2XU, UK.
FAU - Bhatia, Shipra
AU  - Bhatia S
FAU - Bengani, Hemant
AU  - Bengani H
FAU - Gautier, Philippe
AU  - Gautier P
FAU - Rainger, Joe
AU  - Rainger J
FAU - Pearson, Matt
AU  - Pearson M
FAU - Ansari, Morad
AU  - Ansari M
FAU - Crow, Jayne
AU  - Crow J
FAU - Mehendale, Felicity
AU  - Mehendale F
FAU - Palinkasova, Bozena
AU  - Palinkasova B
FAU - Dixon, Michael J
AU  - Dixon MJ
FAU - Thompson, Pamela J
AU  - Thompson PJ
FAU - Matarin, Mar
AU  - Matarin M
FAU - Sisodiya, Sanjay M
AU  - Sisodiya SM
FAU - Kleinjan, Dirk A
AU  - Kleinjan DA
FAU - Fitzpatrick, David R
AU  - Fitzpatrick DR
LA  - eng
GR  - MC_PC_U127561093/MRC_/Medical Research Council/United Kingdom
GR  - MC_U127561093/MRC_/Medical Research Council/United Kingdom
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131220
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Matrix Attachment Region Binding Proteins)
RN  - 0 (SATB2 protein, human)
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (SOX9 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Child
MH  - Child, Preschool
MH  - Epistasis, Genetic
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Matrix Attachment Region Binding Proteins/*genetics
MH  - Mice
MH  - Mutation
MH  - Pierre Robin Syndrome/*diagnosis/genetics
MH  - Regulatory Elements, Transcriptional
MH  - SOX9 Transcription Factor/*genetics
MH  - Transcription Factors/*genetics
MH  - Young Adult
MH  - Zebrafish
PMC - PMC3990159
EDAT- 2013/12/24 06:00
MHDA- 2014/12/15 06:00
PMCR- 2013/12/20
CRDT- 2013/12/24 06:00
PHST- 2013/12/24 06:00 [entrez]
PHST- 2013/12/24 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2013/12/20 00:00 [pmc-release]
AID - ddt647 [pii]
AID - 10.1093/hmg/ddt647 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2014 May 15;23(10):2569-79. doi: 10.1093/hmg/ddt647. Epub 2013 Dec 
      20.