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MeCP2, A Modulator of Neuronal Chromatin Organization Involved in Rett Syndrome

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Neuroepigenomics in Aging and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 978))

Abstract

From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners. The final outcome is a highly specialized chromatin organization wherein linker histones (histones of the H1 family) and MeCP2 share an organizational role that dynamically changes during neuronal development and that it is still poorly understood. MeCP2 mutations alter its chromatin-binding dynamics and/or impair the ability of the protein to interact with some of its partners, resulting in Rett syndrome (RTT). Therefore, deciphering the molecular details involved in the MeCP2 neuronal chromatin arrangement is critical for our understanding of the proper and altered functionality of these cells.

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Abbreviations

AFM:

Atomic force microscopy

ATRX:

α-Thalassemia mental retardation X linked

ChIP-seq:

Chromatin immunoprecipitation and sequencing

CREB:

cAMP response element-binding protein

CTCF:

CCCTC-binding factor

CTD:

C-terminal domain

Dlk1:

Delta-like 1 homolog (Drosophila)

Dlx:

Distal-less homeobox

DNMT:

DNA (cytosine-5)-methyltransferase 1

Gtl2:

Gene trap locus 2

HDAC:

Histone deacetylases

ICR:

Imprinting control region

ID:

Intervening domain

IDP:

Intrinsically disordered protein

Igf2:

Insulin-like growth factor 2

MBD:

Methyl-binding domain

MeCp2:

Methyl CpG binding protein

MoRF:

Molecular recognition features

N-CoR:

Nuclear receptor corepressor 1

NCP:

Nucleosome core particle

NLS:

nuclear localization signal

NRL:

Nucleosome repeat length

NTD:

N-terminal domain

PTM:

Posttranslational modification

RTT:

Rett syndrome

SIN3A:

Switch-independent 3a

TET:

Ten-eleven translocation

TRD:

Transcriptional repressor domain

WDR:

WW domain-binding region

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Acknowledgments

This work was supported by a Canadian Institutes of Health Research (CIHR) MOP-97878 grant to JA.

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  1. Department of Biochemistry and Microbiology, University of Victoria, Petch Building 258-260, Victoria, BC, V8W 3P6, Canada

    Alexia Martínez de Paz & Juan Ausió

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  1. Alexia Martínez de Paz
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  2. Juan Ausió
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Correspondence to Juan Ausió .

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  1. Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), CATALONIA, Spain

    Raul Delgado-Morales

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Martínez de Paz, A., Ausió, J. (2017). MeCP2, A Modulator of Neuronal Chromatin Organization Involved in Rett Syndrome. In: Delgado-Morales, R. (eds) Neuroepigenomics in Aging and Disease. Advances in Experimental Medicine and Biology(), vol 978. Springer, Cham. https://doi.org/10.1007/978-3-319-53889-1_1

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