PMID- 31671722
OWN - NLM
STAT- MEDLINE
DCOM- 20200327
LR  - 20240214
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 21
DP  - 2019 Oct 29
TI  - ATRX Contributes to MeCP2-Mediated Pericentric Heterochromatin Organization 
      during Neural Differentiation.
LID - 10.3390/ijms20215371 [doi]
LID - 5371
AB  - Methyl-CpG binding protein 2 (MeCP2) is a multi-function factor involved in 
      locus-specific transcriptional modulation and the regulation of genome 
      architecture, e.g., pericentric heterochromatin (PCH) organization. MECP2 
      mutations are responsible for Rett syndrome (RTT), a devastating postnatal 
      neurodevelopmental disorder, the pathogenetic mechanisms of which are still 
      unknown. MeCP2, together with Alpha-thalassemia/mental retardation syndrome 
      X-linked protein (ATRX), accumulates at chromocenters, which are repressive PCH 
      domains. As with MECP2, mutations in ATRX cause ATR-X syndrome which is 
      associated with severe intellectual disability. We exploited two murine embryonic 
      stem cell lines, in which the expression of MeCP2 or ATRX is abolished. Through 
      immunostaining, chromatin immunoprecipitation and western blot, we show that 
      MeCP2 and ATRX are reciprocally dependent both for their expression and targeting 
      to chromocenters. Moreover, ATRX plays a role in the accumulation of members of 
      the heterochromatin protein 1 (HP1) family at PCH and, as MeCP2, modulates their 
      expression. Furthermore, ATRX and HP1 targeting to chromocenters depends on an 
      RNA component. 3D-DNA fluorescence in situ hybridization (FISH) highlighted, for 
      the first time, a contribution of ATRX in MeCP2-mediated chromocenter clustering 
      during neural differentiation. Overall, we provide a detailed dissection of the 
      functional interplay between MeCP2 and ATRX in higher-order PCH organization in 
      neurons. Our findings suggest molecular defects common to RTT and ATR-X syndrome, 
      including an alteration in PCH.
FAU - Marano, Domenico
AU  - Marano D
AUID- ORCID: 0000-0003-0224-8870
AD  - Institute of Genetics and Biophysics 'A. Buzzati-Traverso', National Research 
      Council (CNR), 80131 Naples, Italy. domenico.marano@igb.cnr.it.
FAU - Fioriniello, Salvatore
AU  - Fioriniello S
AUID- ORCID: 0000-0003-1345-4434
AD  - Institute of Genetics and Biophysics 'A. Buzzati-Traverso', National Research 
      Council (CNR), 80131 Naples, Italy. salvatore.fioriniello@igb.cnr.it.
FAU - Fiorillo, Francesca
AU  - Fiorillo F
AD  - Institute of Genetics and Biophysics 'A. Buzzati-Traverso', National Research 
      Council (CNR), 80131 Naples, Italy. francesca.fiorillo@igb.cnr.it.
FAU - Gibbons, Richard J
AU  - Gibbons RJ
AD  - MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, 
      University of Oxford, Oxford OX3 9DS, UK. richard.gibbons@imm.ox.ac.uk.
FAU - D'Esposito, Maurizio
AU  - D'Esposito M
AUID- ORCID: 0000-0003-4783-7572
AD  - Institute of Genetics and Biophysics 'A. Buzzati-Traverso', National Research 
      Council (CNR), 80131 Naples, Italy. maurizio.desposito@igb.cnr.it.
FAU - Della Ragione, Floriana
AU  - Della Ragione F
AUID- ORCID: 0000-0003-1643-6418
AD  - Institute of Genetics and Biophysics 'A. Buzzati-Traverso', National Research 
      Council (CNR), 80131 Naples, Italy. floriana.dellaragione@igb.cnr.it.
LA  - eng
GR  - MC_UU_00016/3/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12009/3/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20191029
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Heterochromatin)
RN  - 0 (Mecp2 protein, mouse)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 107283-02-3 (Chromobox Protein Homolog 5)
RN  - EC 3.6.4.12 (Atrx protein, mouse)
RN  - EC 3.6.4.12 (X-linked Nuclear Protein)
RN  - ATR-X syndrome
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics/*physiology
MH  - Chromobox Protein Homolog 5
MH  - Chromosomal Proteins, Non-Histone/genetics/metabolism
MH  - Disease Models, Animal
MH  - Embryonic Stem Cells
MH  - Gene Expression Regulation
MH  - Gene Knockout Techniques
MH  - Heterochromatin/chemistry/genetics/*metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Intellectual Disability/genetics
MH  - Mental Retardation, X-Linked/genetics
MH  - Methyl-CpG-Binding Protein 2/genetics/*metabolism
MH  - Mice
MH  - Mutation
MH  - Neurons/*metabolism
MH  - Rett Syndrome/genetics
MH  - X-linked Nuclear Protein/chemistry/genetics/*metabolism
MH  - alpha-Thalassemia/genetics
PMC - PMC6862095
OTO - NOTNLM
OT  - ATRX
OT  - HP1
OT  - MECP2
OT  - Rett syndrome
OT  - neurons
OT  - pericentric heterochromatin
COIS- The authors declare no conflict of interest.
EDAT- 2019/11/02 06:00
MHDA- 2020/03/28 06:00
PMCR- 2019/11/01
CRDT- 2019/11/02 06:00
PHST- 2019/10/15 00:00 [received]
PHST- 2019/10/24 00:00 [accepted]
PHST- 2019/11/02 06:00 [entrez]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2020/03/28 06:00 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - ijms20215371 [pii]
AID - ijms-20-05371 [pii]
AID - 10.3390/ijms20215371 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Oct 29;20(21):5371. doi: 10.3390/ijms20215371.