Etudes sur le mécanisme de remodelage des nucléosomes par ...
Etudes sur le mécanisme de remodelage des nucléosomes par ...
Etudes sur le mécanisme de remodelage des nucléosomes par ...
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tel-00413908, version 1 - 7 Sep 2009<br />
2000). CHD2 is highly related to CHD1. Yoo et al., (2000) reported another CHD-type<br />
ATPase in fission yeast, cal<strong>le</strong>d as Hrp1, and found it to be involved in chromosome<br />
con<strong>de</strong>nsation during mitosis. CHD3 (Mi-2a) and CHD4 (Mi-2b) contains two PHD fingers.<br />
Mi-2 comp<strong>le</strong>xes are also cal<strong>le</strong>d as NURD (NUc<strong>le</strong>osome Remo<strong>de</strong>ling and Deacetylation) due<br />
to the subunit composition of the comp<strong>le</strong>xes. (See figure I.20 for their subunit composition,<br />
homologous and shared subunits among different species). These comp<strong>le</strong>xes contain<br />
HDAC1/2 as subunits (Keh<strong>le</strong> et al., 1998; Wa<strong>de</strong> et al., 1998). Besi<strong>de</strong>s ATPase and HDAC<br />
modu<strong>le</strong>s, two additional proteins are found in the human NURD comp<strong>le</strong>xes: MTA-1 and<br />
MTA-2 (Metastasis Associated Antigens). MTA-2 is a 70 kDa protein and is highly<br />
associated to MTA-1 and is essential for efficient <strong>de</strong>acetylase activity of the comp<strong>le</strong>x (Xue et<br />
al., 1998; Zhang et al., 1999). Since hypoacetylated histones are known to be associated with<br />
repression of transcription, these comp<strong>le</strong>xes are thought to be involved in gene si<strong>le</strong>ncing.<br />
Moreover, it contains another subunit MBD3 which is highly related to methyl cytosine<br />
binding protein, MBD2 (Wa<strong>de</strong> et al., 1999). Furthermore, MBD2 itself can associate with the<br />
comp<strong>le</strong>x and form a chromatin remo<strong>de</strong>ling comp<strong>le</strong>x (formally cal<strong>le</strong>d as MeCP1 comp<strong>le</strong>x)<br />
which preferentially binds to CpG islands of methylated DNA (Ng and Bird, 1999; Feng and<br />
Zhang, 2001). This indicates their ro<strong>le</strong> in coordinating histone <strong>de</strong>acetylation with DNA<br />
methylation during gene si<strong>le</strong>ncing. In addition, they are also involved in several other<br />
repression processes in cells such as repression of homeotic genes during <strong>de</strong>velopment (Keh<strong>le</strong><br />
et al., 1998), cell-type specific regulation of genes in lymphocytes (Kim et al., 1999; Cobb et<br />
al., 2000) and regulation of cell cyc<strong>le</strong> through human papillomaviruses (Brehm et al., 1999).<br />
Figure I.20 Subunit compositions of CHD subfamily members. The catalytic subunit is marked by<br />
an asterisk and subunits which are homologous in different organisms by virtue of their sequence are<br />
shadowed in grey. Adapted from Gangaraju and Bartholomew, 2007.<br />
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