To our knowledge, this is the first demonstration that an hypomorphic variant of a transcription factor might influence CKD progression, by modulating, likely through chromatin modification, the expression of target genes, i.e. Tgfa (Fig 9).
Recently, it has been demonstrated that YEATS2 interacts with the Ada-Two-A-Containing complex (Wang et al., 2008), which, together with Spt-Ada-Gcn5-Acetyl-Transferase, is able to modulate transcription, both by causing chromatin modification and by interacting with the TATA-binding proteins (Krebs et al., 2011; Wang et al., 2008).
Such modifications can modulate chromatin structure, and they can be recognized by specific proteins or protein domains.
Histone acetylation, to be sure, is only one of several histones and DNA covalent modifications that modulate chromatin topology – the so called "epigenome".
Though the mechanisms governing nuclear organization are not well understood, it is apparent that epigenetic modifications coordinately modulate chromatin organization as well as transcription.
ISWI complexes are recruited to their nucleosomal substrates through their interactions with DNA-binding domains with the extranucleosomal DNA and/or by recognizing histone modifications to modulate chromatin structure [ 43, 44].
For instance, both chromatin modification and microRNAs modulate AS (Kalsotra et al., 2010; Luco et al., 2010).
Small RNAs regulate gene expression by modulating mRNA degradation, translational repression, and chromatin modification [ 1- 6].
Chromatin structure is dynamically modulated by various chromatin modifications, such as histone/DNA methylation and demethylation.
The mechanisms by which trxG complexes modulate chromatin structure include both non-covalent, ATP-dependent nucleosome sliding and covalent modification of histone tails.
