CEBPA (CCAAT/enhancer binding protein (C/EBP), alpha)

	Figure 1: Human C/EBPa mRNA.
Description	Human C/EBPα is an intronless gene located on the minus strand of chromosome 19q.
Transcription	The C/EBPa mRNA (RNA messenger) consists of a short 5' unstranslated region (5'-UTR), a unique protein coding sequence (CDS) and a long 3'-UTR (Hendricks-Taylor et al., 1992).

	Figure 2: C/EBPa protein domains and interactions.
Description	Human C/EBPα mRNA gives rise to two protein products by using two different translation starting sites (Figure 1 and 2) (Calkhoven et al., 2000). Compared to full-length C/EBPA protein, P42, the shorter P30 isoform lacks N-terminal 117 amino acids (Lin et al., 1993). As a transcription factor, C/EBPA protein consists of DNA-binding domain (DBD) in its carboxyl-terminal (C-terminal), which is conserved between C/ebp family members (Leutz et al., 2011). The highly conserved C-terminus includes the basic DNA binding leucine zipper domain (bZip). The bZip domain in turn consists of a basic region that represents the DNA binding domain (DBD), the fork domain and the leucine zipper domain (LZ). The bZip domain is indispensable for homodimerization and heterodimerization with other members of the C/EBP family. This region is also involved in the interaction with other transcription factors (e.g. E2F, PU.1, c-JUN, RUNX1 and ETS1) (McNagny et al., 1998; Yamaguchi et al., 1999; Ramji and Foka, 2002; Nerlov, 2004; Koschmieder et al., 2005; Leutz et al., 2011). The N-terminus of C/EBPa consists of three transactivation domains (TA), which can interact with components of the transcriptional machinery (e.g. CBP/P300, TBP/TFIIB) (Nerlov and Ziff, 1995; Kovacs et al., 2003; Schwartz et al., 2003), cell cycle regulators (e.g. E2F, CDK2, CDK4) (Porse et al., 2001; Porse et al., 2006) and chromatin remodellers (e.g. SWI/SNF) (Pedersen et al., 2001).
Expression	C/EBPa is mainly expressed in terminally differentiated cells, such as mature adipocytes and myelomonocytic cells. C/EBPa is also found expressed in skin, intestine, lung, adrenal gland, mammary gland, ovary, prostate, placenta (Oh and Smart, 1998; Birkenmeier et al., 1989).
Localisation	C/EBPa protein is localized in nucleus.
Function	C/EBPa homozygous null mice lack white adipose tissues (Wang et al., 1995), as well as mature granulocytes and granulocyte-macrophage precursors (Zhang et al., 1997; Heath et al., 2004). In addition, forced expression of C/EBPa can direct uncommitted progenitors to differentiate into adipocytes and granulocytes (Freytag et al., 1994; Radomska et al., 1998; Nerlov et al., 1998). Further studies suggest that C/EBPa plays important roles in lineage determination by activating lineage-specific genes (Nerlov, 2004; Graf and Enver, 2009). In hematopoiesis, C/EBPa is one of the key factors driving myeloid cell differentiation from hematopoietic stem cells by interacting with other proteins, such as the ETS family transcription factor PU.1, the ATP dependent chromatin remodeling complex SWI/SNF, the DNA modifying enzyme TET2 (McNagny et al., 1998; Koschmieder et al., 2005; Leutz et al., 2011; Kallin et al., 2012). Ectopic expression of C/EBPa leads to cell cycle arrest via direct interaction with the key cell cycle regulators CDK2/4 and E2F (Porse et al., 2001; Porse et al., 2006). The N-terminal truncated form of C/EBPa, P30, has been shown to act as a dominant negative regulator of the full-length form, P42. Modulation of P30 expression level in mice can alter normal adipogenesis and granulopoiesis (Kirstetter et al., 2008). Notably, ectopic expression of C/EBPa in B and T-lymphocyte precursors results in transdifferentiation into functional macrophages (Xie et al., 2004; Laiosa et al., 2006; Bussmann et al., 2009; Di Tullio et al., 2011; Kallin et al., 2012). Interestingly, C/EBPa mediated conversion of B lymphoma cells into macrophages impairs significantly its tumorigenicity, providing a novel strategy for lymphoma treatment (Rapino et al., 2013). Moreover, a recent study showed that transient C/EBPa expression is also capable of facilitating the conversion of B cells into induced pluripotent stem cells (iPS cells) (Di Stefano et al., 2014). Moreover, C/EBPa has been shown involved in lung development and airway epithelial differentiation (Cassel et al., 2000a; Cassel et al., 2000b; Cassel et al., 2002). The conditional deletion of C/EBPa gene in respiratory epithelium results in respiratory arrest and death soon after birth. This phenotype is associated with proliferation of immature type II alveolar cells, which causes epithelial expansion and loss of air space (Martis et al., 2006; Basseres et al., 2006).
Homology	C/EBPa belongs to the CCAAT/enhancer binging protein family and is highly conserved across vertebrate species. Sequence alignments show that C/EBP members share several conserved regions including the bZip and transactivation domains (Leutz et al., 2011).

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